{"search_session":{},"preferences":{"l":"en","queryLanguage":"en"},"patentId":"US_7094801_B2","frontPageModel":{"patentViewModel":{"ref":{"entityRefType":"PATENT","entityRefId":"111-352-037-735-89X"},"entityMetadata":{"linkedIds":{"empty":true},"tags":[],"collections":[{"id":22716,"type":"PATENT","title":"Citing Erasmus Univ Rotterdam publications","description":"Patent documents citing scholarly work of Erasmus Univ Rotterdam","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":18694,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:36:34Z","updated":"2017-08-07T04:36:34Z","lastEventDate":"2017-08-07T04:36:34Z"},{"id":22722,"type":"PATENT","title":"Citing ICSTM publications","description":"Patent documents citing scholarly work of ICSTM","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":51214,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:40:07Z","updated":"2017-08-07T04:40:07Z","lastEventDate":"2017-08-07T04:40:07Z"},{"id":22724,"type":"PATENT","title":"Citing Univ Wurzburg publications","description":"Patent documents citing scholarly work of Univ Wurzburg","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":15059,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:41:01Z","updated":"2017-08-07T04:41:01Z","lastEventDate":"2017-08-07T04:41:01Z"},{"id":22729,"type":"PATENT","title":"Citing UC Los Angeles publications","description":"Patent documents citing scholarly work of UC Los Angeles","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":73948,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:42:18Z","updated":"2017-08-07T04:42:18Z","lastEventDate":"2017-08-07T04:42:18Z"},{"id":22730,"type":"PATENT","title":"Citing Univ Colorado Boulder publications","description":"Patent documents citing scholarly work of Univ Colorado Boulder","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":40438,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:43:21Z","updated":"2017-08-07T04:43:21Z","lastEventDate":"2017-08-07T04:43:21Z"},{"id":22735,"type":"PATENT","title":"Citing Tohoku Univ publications","description":"Patent documents citing scholarly work of Tohoku Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":26893,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:45:26Z","updated":"2017-08-07T04:45:26Z","lastEventDate":"2017-08-07T04:45:26Z"},{"id":22739,"type":"PATENT","title":"Citing KU Leuven publications","description":"Patent documents citing scholarly work of KU Leuven","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":30113,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:46:44Z","updated":"2017-08-07T04:46:44Z","lastEventDate":"2017-08-07T04:46:44Z"},{"id":22754,"type":"PATENT","title":"Citing Univ Copenhagen publications","description":"Patent documents citing scholarly work of Univ Copenhagen","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":27948,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:51:13Z","updated":"2017-08-07T04:51:13Z","lastEventDate":"2017-08-07T04:51:13Z"},{"id":22763,"type":"PATENT","title":"Citing NYU publications","description":"Patent documents citing scholarly work of NYU","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":34711,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:55:15Z","updated":"2017-08-07T04:55:15Z","lastEventDate":"2017-08-07T04:55:15Z"},{"id":22766,"type":"PATENT","title":"Citing McGill Univ publications","description":"Patent documents citing scholarly work of McGill Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":33777,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:56:02Z","updated":"2017-08-07T04:56:02Z","lastEventDate":"2017-08-07T04:56:02Z"},{"id":22772,"type":"PATENT","title":"Citing UT Southwestern Medical Center publications","description":"Patent documents citing scholarly work of UT Southwestern Medical Center","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":33567,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:58:18Z","updated":"2017-08-07T04:58:18Z","lastEventDate":"2017-08-07T04:58:18Z"},{"id":22773,"type":"PATENT","title":"Citing Univ Washington publications","description":"Patent documents citing scholarly work of Univ Washington","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":75126,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:58:47Z","updated":"2017-08-07T04:58:47Z","lastEventDate":"2017-08-07T04:58:47Z"},{"id":22789,"type":"PATENT","title":"Citing NUS publications","description":"Patent documents citing scholarly work of NUS","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":19273,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:05:12Z","updated":"2017-08-07T05:05:12Z","lastEventDate":"2017-08-07T05:05:12Z"},{"id":22799,"type":"PATENT","title":"Citing Univ Alabama System publications","description":"Patent documents citing scholarly work of Univ Alabama System","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":32860,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:09:26Z","updated":"2017-08-07T05:09:26Z","lastEventDate":"2017-08-07T05:09:26Z"},{"id":22800,"type":"PATENT","title":"Citing Baylor College Med publications","description":"Patent documents citing scholarly work of Baylor College Med","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":37085,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:09:55Z","updated":"2017-08-07T05:09:55Z","lastEventDate":"2017-08-07T05:09:55Z"},{"id":22801,"type":"PATENT","title":"Citing Univ Montpellier publications","description":"Patent documents citing scholarly work of Univ Montpellier","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":12183,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:10:27Z","updated":"2017-08-07T05:10:27Z","lastEventDate":"2017-08-07T05:10:27Z"},{"id":22802,"type":"PATENT","title":"Citing UC System publications","description":"Patent documents citing scholarly work of UC System","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":266608,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:10:38Z","updated":"2017-08-07T05:10:38Z","lastEventDate":"2017-08-07T05:10:38Z"},{"id":22804,"type":"PATENT","title":"Citing Univ Michigan publications","description":"Patent documents citing scholarly work of Univ Michigan","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":66705,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:14:35Z","updated":"2017-08-07T05:14:35Z","lastEventDate":"2017-08-07T05:14:35Z"},{"id":22811,"type":"PATENT","title":"Citing Univ Pennsylvania publications","description":"Patent documents citing scholarly work of Univ Pennsylvania","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":65126,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:17:40Z","updated":"2017-08-07T05:17:40Z","lastEventDate":"2017-08-07T05:17:40Z"},{"id":22820,"type":"PATENT","title":"Citing Univ Groningen publications","description":"Patent documents citing scholarly work of Univ Groningen","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":21355,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:20:46Z","updated":"2017-08-07T05:20:46Z","lastEventDate":"2017-08-07T05:20:46Z"},{"id":22831,"type":"PATENT","title":"Citing Univ Minnesota Twin Cities publications","description":"Patent documents citing scholarly work of Univ Minnesota Twin Cities","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":52155,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:24:37Z","updated":"2017-08-07T05:24:37Z","lastEventDate":"2017-08-07T05:24:37Z"},{"id":22841,"type":"PATENT","title":"Citing Osaka Univ publications","description":"Patent documents citing scholarly work of Osaka Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":46815,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:27:12Z","updated":"2017-08-07T05:27:12Z","lastEventDate":"2017-08-07T05:27:12Z"},{"id":22845,"type":"PATENT","title":"Citing Uppsala Univ publications","description":"Patent documents citing scholarly work of Uppsala Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":24847,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:29:57Z","updated":"2017-08-07T05:29:57Z","lastEventDate":"2017-08-07T05:29:57Z"},{"id":22852,"type":"PATENT","title":"Citing Univ Oxford publications","description":"Patent documents citing scholarly work of Univ Oxford","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":51799,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:33:16Z","updated":"2017-08-07T05:33:16Z","lastEventDate":"2017-08-07T05:33:16Z"},{"id":22855,"type":"PATENT","title":"Citing University College London (UCL) publications","description":"Patent documents citing scholarly work of University College London (UCL)","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":53487,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:34:28Z","updated":"2017-08-07T05:34:28Z","lastEventDate":"2017-08-07T05:34:28Z"},{"id":22856,"type":"PATENT","title":"Citing NIH publications","description":"Patent documents citing scholarly work of NIH","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":151649,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:35:15Z","updated":"2017-08-07T05:35:15Z","lastEventDate":"2017-08-07T05:35:15Z"},{"id":22859,"type":"PATENT","title":"Citing Harvard Univ publications","description":"Patent documents citing scholarly work of Harvard Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":175224,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:37:44Z","updated":"2017-08-07T05:37:44Z","lastEventDate":"2017-08-07T05:37:44Z"},{"id":22860,"type":"PATENT","title":"Citing UC San Diego publications","description":"Patent documents citing scholarly work of UC San Diego","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":70050,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:40:14Z","updated":"2017-08-07T05:40:14Z","lastEventDate":"2017-08-07T05:40:14Z"},{"id":22864,"type":"PATENT","title":"Citing Ohio State Univ publications","description":"Patent documents citing scholarly work of Ohio State Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":31507,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:42:04Z","updated":"2017-08-07T05:42:04Z","lastEventDate":"2017-08-07T05:42:04Z"},{"id":22871,"type":"PATENT","title":"Citing Univ Aix-Marseille publications","description":"Patent documents citing scholarly work of Univ Aix-Marseille","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":12318,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:44:42Z","updated":"2017-08-07T05:44:42Z","lastEventDate":"2017-08-07T05:44:42Z"},{"id":22878,"type":"PATENT","title":"Citing Univ London publications","description":"Patent documents citing scholarly work of Univ London","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":96093,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:47:35Z","updated":"2017-08-07T05:47:35Z","lastEventDate":"2017-08-07T05:47:35Z"},{"id":22880,"type":"PATENT","title":"Citing Univ Helsinki publications","description":"Patent documents citing scholarly work of Univ Helsinki","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":23116,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:49:16Z","updated":"2017-08-07T05:49:16Z","lastEventDate":"2017-08-07T05:49:16Z"},{"id":22886,"type":"PATENT","title":"Citing Univ Texas System publications","description":"Patent documents citing scholarly work of Univ Texas System","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":110344,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:51:34Z","updated":"2017-08-07T05:51:34Z","lastEventDate":"2017-08-07T05:51:34Z"},{"id":22899,"type":"PATENT","title":"Citing Univ Rochester publications","description":"Patent documents citing scholarly work of Univ Rochester","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":24884,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:56:06Z","updated":"2017-08-07T05:56:06Z","lastEventDate":"2017-08-07T05:56:06Z"},{"id":22901,"type":"PATENT","title":"Citing Johns Hopkins Univ publications","description":"Patent documents citing scholarly work of Johns Hopkins Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":76487,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:56:37Z","updated":"2017-08-07T05:56:37Z","lastEventDate":"2017-08-07T05:56:37Z"},{"id":22903,"type":"PATENT","title":"Citing Kings College London publications","description":"Patent documents citing scholarly work of Kings College London","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":26647,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:58:18Z","updated":"2017-08-07T05:58:18Z","lastEventDate":"2017-08-07T05:58:18Z"},{"id":27083,"type":"PATENT","title":"Patents citing scholarly work funded by Wellcome Trust","description":"","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":45204,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2018-01-23T03:10:18Z","updated":"2018-01-23T03:17:28Z","lastEventDate":"2018-01-23T03:17:28Z"},{"id":184966,"type":"PATENT","title":"Búsqueda 15","description":"((Antimicrobial) AND (antifung* OR fungicide) AND (\"Vehicle of active substances\" OR Carrier OR \"active mat*\" OR Diffusor OR \"Active membrane\") AND (electrospinnig OR Electrohydrodynamic OR Electrospun OR entrapment OR scaffold OR immobilized OR encapsulat* OR nanoencapsulat* OR \"Electrostatic spuinning\") AND (\"Essential Oil\" OR \"plant extract\" OR extract OR bioparticle))\n**8619**","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":8619,"tags":[],"user":{"id":375402790,"username":"la_cabrera10","firstName":"","lastName":"","created":"2020-10-29T22:03:42.000Z","displayName":"la_cabrera10","preferences":"{\"usage\":\"public\"}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2020-10-30T00:10:44Z","updated":"2020-10-30T00:11:14Z","lastEventDate":"2020-10-30T00:11:14Z"},{"id":191233,"type":"PATENT","title":"AdhesionCellANDsubstrateANDcancercellANDtio2","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":22103,"tags":[],"user":{"id":404574126,"username":"JaimeGarcia","firstName":"","lastName":"","created":"2021-05-17T13:10:07.000Z","displayName":"JaimeGarcia","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2021-05-17T14:17:38Z","updated":"2021-10-22T12:32:49Z","lastEventDate":"2021-10-22T12:32:49Z"},{"id":191394,"type":"PATENT","title":"DeviceLensVsOrbit","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":true,"savedQueries":[],"created":"2021-05-23T03:40:59Z","updated":"2021-05-23T03:41:04Z","lastEventDate":"2021-05-23T03:41:04Z"},{"id":191423,"type":"PATENT","title":"Patent (Cell adhesion) AND substrate AND (cancer cell) AND (titanium dioxide) AND coating","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":21074,"tags":[],"user":{"id":404574126,"username":"JaimeGarcia","firstName":"","lastName":"","created":"2021-05-17T13:10:07.000Z","displayName":"JaimeGarcia","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2021-05-24T21:41:57Z","updated":"2021-10-22T11:35:59Z","lastEventDate":"2021-10-22T11:35:59Z"},{"id":191790,"type":"PATENT","title":"Busqueda device patent 1","description":"( pancreatic ( islet ( transplantation OR ( pancreatic ( islet cell ) ) ) ) ) AND ( cell ( encapsulation OR encapsulation ) )","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2021-06-04T14:17:19Z","updated":"2021-06-04T14:17:23Z","lastEventDate":"2021-06-04T14:17:23Z"},{"id":191900,"type":"PATENT","title":"CELL ENCAP","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":true,"savedQueries":[],"created":"2021-06-08T19:02:57Z","updated":"2021-10-22T12:44:58Z","lastEventDate":"2021-10-22T12:44:58Z"},{"id":191969,"type":"PATENT","title":"PIT-PIC-CE-E","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":true,"savedQueries":[],"created":"2021-06-11T14:28:04Z","updated":"2021-06-11T14:28:09Z","lastEventDate":"2021-06-11T14:28:09Z"},{"id":191971,"type":"PATENT","title":"PIT-PIC-CE-E","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":true,"savedQueries":[],"created":"2021-06-11T15:34:20Z","updated":"2021-06-11T15:34:23Z","lastEventDate":"2021-06-11T15:34:23Z"},{"id":196689,"type":"PATENT","title":"No33","description":"","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":50000,"tags":[],"user":{"id":418845198,"username":"isanejad","firstName":"","lastName":"","created":"2021-09-04T10:31:19.000Z","displayName":"isanejad","preferences":"{\"beta\":true,\"usage\":\"public\"}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2021-11-16T07:47:24Z","updated":"2021-11-16T07:48:30Z","lastEventDate":"2021-11-16T07:48:30Z"},{"id":213961,"type":"PATENT","title":"CAPSAICIN","description":"","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":34819,"tags":[],"user":{"id":311989179,"username":"xavier.v","firstName":"","lastName":"","created":"2019-04-04T07:03:05.000Z","displayName":"xavier.v","preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2023-10-24T10:33:37Z","updated":"2023-10-24T10:33:39Z","lastEventDate":"2023-10-24T10:33:39Z"}],"notes":[],"inventorships":[],"privateCollections":[],"publicCollections":[{"id":22716,"type":"PATENT","title":"Citing Erasmus Univ Rotterdam publications","description":"Patent documents citing scholarly work of Erasmus Univ Rotterdam","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":18694,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:36:34Z","updated":"2017-08-07T04:36:34Z","lastEventDate":"2017-08-07T04:36:34Z"},{"id":22722,"type":"PATENT","title":"Citing ICSTM publications","description":"Patent documents citing scholarly work of ICSTM","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":51214,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:40:07Z","updated":"2017-08-07T04:40:07Z","lastEventDate":"2017-08-07T04:40:07Z"},{"id":22724,"type":"PATENT","title":"Citing Univ Wurzburg publications","description":"Patent documents citing scholarly work of Univ Wurzburg","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":15059,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:41:01Z","updated":"2017-08-07T04:41:01Z","lastEventDate":"2017-08-07T04:41:01Z"},{"id":22729,"type":"PATENT","title":"Citing UC Los Angeles publications","description":"Patent documents citing scholarly work of UC Los Angeles","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":73948,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:42:18Z","updated":"2017-08-07T04:42:18Z","lastEventDate":"2017-08-07T04:42:18Z"},{"id":22730,"type":"PATENT","title":"Citing Univ Colorado Boulder publications","description":"Patent documents citing scholarly work of Univ Colorado Boulder","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":40438,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:43:21Z","updated":"2017-08-07T04:43:21Z","lastEventDate":"2017-08-07T04:43:21Z"},{"id":22735,"type":"PATENT","title":"Citing Tohoku Univ publications","description":"Patent documents citing scholarly work of Tohoku Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":26893,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:45:26Z","updated":"2017-08-07T04:45:26Z","lastEventDate":"2017-08-07T04:45:26Z"},{"id":22739,"type":"PATENT","title":"Citing KU Leuven publications","description":"Patent documents citing scholarly work of KU Leuven","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":30113,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:46:44Z","updated":"2017-08-07T04:46:44Z","lastEventDate":"2017-08-07T04:46:44Z"},{"id":22754,"type":"PATENT","title":"Citing Univ Copenhagen publications","description":"Patent documents citing scholarly work of Univ Copenhagen","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":27948,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:51:13Z","updated":"2017-08-07T04:51:13Z","lastEventDate":"2017-08-07T04:51:13Z"},{"id":22763,"type":"PATENT","title":"Citing NYU publications","description":"Patent documents citing scholarly work of NYU","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":34711,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:55:15Z","updated":"2017-08-07T04:55:15Z","lastEventDate":"2017-08-07T04:55:15Z"},{"id":22766,"type":"PATENT","title":"Citing McGill Univ publications","description":"Patent documents citing scholarly work of McGill Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":33777,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:56:02Z","updated":"2017-08-07T04:56:02Z","lastEventDate":"2017-08-07T04:56:02Z"},{"id":22772,"type":"PATENT","title":"Citing UT Southwestern Medical Center publications","description":"Patent documents citing scholarly work of UT Southwestern Medical Center","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":33567,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:58:18Z","updated":"2017-08-07T04:58:18Z","lastEventDate":"2017-08-07T04:58:18Z"},{"id":22773,"type":"PATENT","title":"Citing Univ Washington publications","description":"Patent documents citing scholarly work of Univ Washington","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":75126,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T04:58:47Z","updated":"2017-08-07T04:58:47Z","lastEventDate":"2017-08-07T04:58:47Z"},{"id":22789,"type":"PATENT","title":"Citing NUS publications","description":"Patent documents citing scholarly work of NUS","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":19273,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:05:12Z","updated":"2017-08-07T05:05:12Z","lastEventDate":"2017-08-07T05:05:12Z"},{"id":22799,"type":"PATENT","title":"Citing Univ Alabama System publications","description":"Patent documents citing scholarly work of Univ Alabama System","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":32860,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:09:26Z","updated":"2017-08-07T05:09:26Z","lastEventDate":"2017-08-07T05:09:26Z"},{"id":22800,"type":"PATENT","title":"Citing Baylor College Med publications","description":"Patent documents citing scholarly work of Baylor College Med","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":37085,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:09:55Z","updated":"2017-08-07T05:09:55Z","lastEventDate":"2017-08-07T05:09:55Z"},{"id":22801,"type":"PATENT","title":"Citing Univ Montpellier publications","description":"Patent documents citing scholarly work of Univ Montpellier","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":12183,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:10:27Z","updated":"2017-08-07T05:10:27Z","lastEventDate":"2017-08-07T05:10:27Z"},{"id":22802,"type":"PATENT","title":"Citing UC System publications","description":"Patent documents citing scholarly work of UC System","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":266608,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:10:38Z","updated":"2017-08-07T05:10:38Z","lastEventDate":"2017-08-07T05:10:38Z"},{"id":22804,"type":"PATENT","title":"Citing Univ Michigan publications","description":"Patent documents citing scholarly work of Univ Michigan","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":66705,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:14:35Z","updated":"2017-08-07T05:14:35Z","lastEventDate":"2017-08-07T05:14:35Z"},{"id":22811,"type":"PATENT","title":"Citing Univ Pennsylvania publications","description":"Patent documents citing scholarly work of Univ Pennsylvania","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":65126,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:17:40Z","updated":"2017-08-07T05:17:40Z","lastEventDate":"2017-08-07T05:17:40Z"},{"id":22820,"type":"PATENT","title":"Citing Univ Groningen publications","description":"Patent documents citing scholarly work of Univ Groningen","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":21355,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:20:46Z","updated":"2017-08-07T05:20:46Z","lastEventDate":"2017-08-07T05:20:46Z"},{"id":22831,"type":"PATENT","title":"Citing Univ Minnesota Twin Cities publications","description":"Patent documents citing scholarly work of Univ Minnesota Twin Cities","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":52155,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:24:37Z","updated":"2017-08-07T05:24:37Z","lastEventDate":"2017-08-07T05:24:37Z"},{"id":22841,"type":"PATENT","title":"Citing Osaka Univ publications","description":"Patent documents citing scholarly work of Osaka Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":46815,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:27:12Z","updated":"2017-08-07T05:27:12Z","lastEventDate":"2017-08-07T05:27:12Z"},{"id":22845,"type":"PATENT","title":"Citing Uppsala Univ publications","description":"Patent documents citing scholarly work of Uppsala Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":24847,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:29:57Z","updated":"2017-08-07T05:29:57Z","lastEventDate":"2017-08-07T05:29:57Z"},{"id":22852,"type":"PATENT","title":"Citing Univ Oxford publications","description":"Patent documents citing scholarly work of Univ Oxford","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":51799,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:33:16Z","updated":"2017-08-07T05:33:16Z","lastEventDate":"2017-08-07T05:33:16Z"},{"id":22855,"type":"PATENT","title":"Citing University College London (UCL) publications","description":"Patent documents citing scholarly work of University College London (UCL)","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":53487,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:34:28Z","updated":"2017-08-07T05:34:28Z","lastEventDate":"2017-08-07T05:34:28Z"},{"id":22856,"type":"PATENT","title":"Citing NIH publications","description":"Patent documents citing scholarly work of NIH","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":151649,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:35:15Z","updated":"2017-08-07T05:35:15Z","lastEventDate":"2017-08-07T05:35:15Z"},{"id":22859,"type":"PATENT","title":"Citing Harvard Univ publications","description":"Patent documents citing scholarly work of Harvard Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":175224,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:37:44Z","updated":"2017-08-07T05:37:44Z","lastEventDate":"2017-08-07T05:37:44Z"},{"id":22860,"type":"PATENT","title":"Citing UC San Diego publications","description":"Patent documents citing scholarly work of UC San Diego","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":70050,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:40:14Z","updated":"2017-08-07T05:40:14Z","lastEventDate":"2017-08-07T05:40:14Z"},{"id":22864,"type":"PATENT","title":"Citing Ohio State Univ publications","description":"Patent documents citing scholarly work of Ohio State Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":31507,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:42:04Z","updated":"2017-08-07T05:42:04Z","lastEventDate":"2017-08-07T05:42:04Z"},{"id":22871,"type":"PATENT","title":"Citing Univ Aix-Marseille publications","description":"Patent documents citing scholarly work of Univ Aix-Marseille","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":12318,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:44:42Z","updated":"2017-08-07T05:44:42Z","lastEventDate":"2017-08-07T05:44:42Z"},{"id":22878,"type":"PATENT","title":"Citing Univ London publications","description":"Patent documents citing scholarly work of Univ London","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":96093,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:47:35Z","updated":"2017-08-07T05:47:35Z","lastEventDate":"2017-08-07T05:47:35Z"},{"id":22880,"type":"PATENT","title":"Citing Univ Helsinki publications","description":"Patent documents citing scholarly work of Univ Helsinki","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":23116,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:49:16Z","updated":"2017-08-07T05:49:16Z","lastEventDate":"2017-08-07T05:49:16Z"},{"id":22886,"type":"PATENT","title":"Citing Univ Texas System publications","description":"Patent documents citing scholarly work of Univ Texas System","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":110344,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:51:34Z","updated":"2017-08-07T05:51:34Z","lastEventDate":"2017-08-07T05:51:34Z"},{"id":22899,"type":"PATENT","title":"Citing Univ Rochester publications","description":"Patent documents citing scholarly work of Univ Rochester","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":24884,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:56:06Z","updated":"2017-08-07T05:56:06Z","lastEventDate":"2017-08-07T05:56:06Z"},{"id":22901,"type":"PATENT","title":"Citing Johns Hopkins Univ publications","description":"Patent documents citing scholarly work of Johns Hopkins Univ","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":76487,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:56:37Z","updated":"2017-08-07T05:56:37Z","lastEventDate":"2017-08-07T05:56:37Z"},{"id":22903,"type":"PATENT","title":"Citing Kings College London publications","description":"Patent documents citing scholarly work of Kings College London","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":26647,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2017-08-07T05:58:18Z","updated":"2017-08-07T05:58:18Z","lastEventDate":"2017-08-07T05:58:18Z"},{"id":27083,"type":"PATENT","title":"Patents citing scholarly work funded by Wellcome Trust","description":"","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":45204,"tags":[],"user":{"id":233682368,"username":"tech","firstName":"The Lens","lastName":"Team","created":"2017-08-06T20:11:49.000Z","displayName":"The Lens Team","profilePictureKey":"lens/users/15eac2a0-031d-4923-92cb-a162e1cb2bbb/profile-picture","preferences":"{\"beta\":true}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2018-01-23T03:10:18Z","updated":"2018-01-23T03:17:28Z","lastEventDate":"2018-01-23T03:17:28Z"},{"id":184966,"type":"PATENT","title":"Búsqueda 15","description":"((Antimicrobial) AND (antifung* OR fungicide) AND (\"Vehicle of active substances\" OR Carrier OR \"active mat*\" OR Diffusor OR \"Active membrane\") AND (electrospinnig OR Electrohydrodynamic OR Electrospun OR entrapment OR scaffold OR immobilized OR encapsulat* OR nanoencapsulat* OR \"Electrostatic spuinning\") AND (\"Essential Oil\" OR \"plant extract\" OR extract OR bioparticle))\n**8619**","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":8619,"tags":[],"user":{"id":375402790,"username":"la_cabrera10","firstName":"","lastName":"","created":"2020-10-29T22:03:42.000Z","displayName":"la_cabrera10","preferences":"{\"usage\":\"public\"}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2020-10-30T00:10:44Z","updated":"2020-10-30T00:11:14Z","lastEventDate":"2020-10-30T00:11:14Z"},{"id":191233,"type":"PATENT","title":"AdhesionCellANDsubstrateANDcancercellANDtio2","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":22103,"tags":[],"user":{"id":404574126,"username":"JaimeGarcia","firstName":"","lastName":"","created":"2021-05-17T13:10:07.000Z","displayName":"JaimeGarcia","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2021-05-17T14:17:38Z","updated":"2021-10-22T12:32:49Z","lastEventDate":"2021-10-22T12:32:49Z"},{"id":191394,"type":"PATENT","title":"DeviceLensVsOrbit","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":true,"savedQueries":[],"created":"2021-05-23T03:40:59Z","updated":"2021-05-23T03:41:04Z","lastEventDate":"2021-05-23T03:41:04Z"},{"id":191423,"type":"PATENT","title":"Patent (Cell adhesion) AND substrate AND (cancer cell) AND (titanium dioxide) AND coating","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":21074,"tags":[],"user":{"id":404574126,"username":"JaimeGarcia","firstName":"","lastName":"","created":"2021-05-17T13:10:07.000Z","displayName":"JaimeGarcia","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2021-05-24T21:41:57Z","updated":"2021-10-22T11:35:59Z","lastEventDate":"2021-10-22T11:35:59Z"},{"id":191790,"type":"PATENT","title":"Busqueda device patent 1","description":"( pancreatic ( islet ( transplantation OR ( pancreatic ( islet cell ) ) ) ) ) AND ( cell ( encapsulation OR encapsulation ) )","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2021-06-04T14:17:19Z","updated":"2021-06-04T14:17:23Z","lastEventDate":"2021-06-04T14:17:23Z"},{"id":191900,"type":"PATENT","title":"CELL ENCAP","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":true,"savedQueries":[],"created":"2021-06-08T19:02:57Z","updated":"2021-10-22T12:44:58Z","lastEventDate":"2021-10-22T12:44:58Z"},{"id":191969,"type":"PATENT","title":"PIT-PIC-CE-E","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":true,"savedQueries":[],"created":"2021-06-11T14:28:04Z","updated":"2021-06-11T14:28:09Z","lastEventDate":"2021-06-11T14:28:09Z"},{"id":191971,"type":"PATENT","title":"PIT-PIC-CE-E","description":"","access":"OPEN_ACCESS","displayAvatar":false,"attested":false,"itemCount":50000,"tags":[],"user":{"id":390700588,"username":"diegot","firstName":"Diego","lastName":"Triviño Bolaños","created":"2021-02-12T02:57:12.000Z","displayName":"Diego Triviño Bolaños","profilePictureKey":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4","avatar":{"id":977,"key":"lens/avatar/92b0de89-d77f-4973-b88a-4a0e06ac93e4"},"preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":true,"savedQueries":[],"created":"2021-06-11T15:34:20Z","updated":"2021-06-11T15:34:23Z","lastEventDate":"2021-06-11T15:34:23Z"},{"id":196689,"type":"PATENT","title":"No33","description":"","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":50000,"tags":[],"user":{"id":418845198,"username":"isanejad","firstName":"","lastName":"","created":"2021-09-04T10:31:19.000Z","displayName":"isanejad","preferences":"{\"beta\":true,\"usage\":\"public\"}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2021-11-16T07:47:24Z","updated":"2021-11-16T07:48:30Z","lastEventDate":"2021-11-16T07:48:30Z"},{"id":213961,"type":"PATENT","title":"CAPSAICIN","description":"","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":34819,"tags":[],"user":{"id":311989179,"username":"xavier.v","firstName":"","lastName":"","created":"2019-04-04T07:03:05.000Z","displayName":"xavier.v","preferences":"{}","accountType":"PERSONAL","isOauthOnly":false},"notes":[],"sharedType":"PUBLISHED","hasLinkedSavedQueries":false,"savedQueries":[],"created":"2023-10-24T10:33:37Z","updated":"2023-10-24T10:33:39Z","lastEventDate":"2023-10-24T10:33:39Z"}],"privateNotes":[],"landscapeCollections":[],"landscapeNotes":[]},"document":{"record_lens_id":"111-352-037-735-89X","lens_id":["111-352-037-735-89X","172-866-147-002-962"],"doc_key":"US_7094801_B2_20060822","created":"2016-01-15T06:56:06.589","docdb_id":287159183,"lens_internal":{"earliest_lens_id_created_time":"2016-01-15T06:56:06.589","last_modified":"2024-03-25T18:53:33.665","legacy_pub_key":"US_7094801_B2","has_doc_lang":true,"has_biblio_lang":true,"has_all_title_lang":true,"has_all_abstract_lang":true,"has_all_claims_lang":true,"has_description_lang":true},"jurisdiction":"US","doc_number":"7094801","kind":"B2","date_published":"2006-08-22","year_published":2006,"ids":["US_7094801_B2","111-352-037-735-89X","172-866-147-002-962","US_7094801_B2_20060822","US","7094801","B2","US7094801B2","US7094801","7094801B2"],"lang":"en","publication_type":"GRANTED_PATENT","application_reference":{"jurisdiction":"US","doc_number":"32498702","kind":"A","date":"2002-12-19"},"priority_claim":[{"jurisdiction":"US","doc_number":"32498702","kind":"A","date":"2002-12-19"},{"jurisdiction":"US","doc_number":"34203401","kind":"P","date":"2001-12-19"},{"jurisdiction":"US","doc_number":"38648202","kind":"P","date":"2002-06-05"}],"priority_claim.source":"DOCDB","earliest_priority_claim_date":"2001-12-19","title":{"en":[{"text":"Chalcone derivatives and their use to treat diseases","lang":"en","source":"DOCDB","data_format":"DOCDBA"}]},"title_lang":["en"],"has_title":true,"applicant":[{"name":"ATHEROGENICS INC","residence":"US","sequence":1,"app_type":"applicant"}],"applicant_count":1,"has_applicant":true,"inventor":[{"name":"SIKORSKI JAMES A","residence":"US","sequence":1},{"name":"MENG CHARLES Q","residence":"US","sequence":2},{"name":"WEINGARTEN M DAVID","residence":"US","sequence":3},{"name":"WORSENCROFT KIMBERLY J","residence":"US","sequence":4},{"name":"NI LIMING","residence":"US","sequence":5}],"inventor_count":5,"has_inventor":true,"agent":[{"name":"Sherry M. Knowles, Esq.","sequence":1},{"name":"King&Spalding, LLP","sequence":2}],"agent_count":2,"has_agent":true,"owner":[{"name":"SALUTRIA PHARMACEUTICALS LLC","address":"8995 WESTSIDE PARKWAY, ALPHARETTA, GEORGIA, 30009","sequence":1,"recorded_date":"2010-09-03","execution_date":"2009-04-01","is_current_owner":true}],"owner_count":1,"owner_all":[{"name":"SALUTRIA PHARMACEUTICALS LLC","address":"8995 WESTSIDE PARKWAY, ALPHARETTA, GEORGIA, 30009","sequence":1,"recorded_date":"2010-09-03","execution_date":"2009-04-01","is_current_owner":true}],"owner_all_count":1,"has_owner":true,"primary_examiner":{"name":"Deborah C. Lambkin","department":"1626"},"has_examiner":true,"class_ipcr":[{"symbol":"A61K31/38","version_indicator":"2006-01-01","class_symbol_position":"F","class_value":"I","action_date":"2006-08-22","class_status":"B","class_data_source":"H","generating_office":"US","sequence":1},{"symbol":"A61K31/341","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":2},{"symbol":"A61K31/381","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":3},{"symbol":"A61K31/40","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2006-08-22","class_status":"B","class_data_source":"H","generating_office":"US","sequence":4},{"symbol":"A61K31/4025","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":5},{"symbol":"A61K31/404","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":6},{"symbol":"A61K31/41","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":7},{"symbol":"A61K31/4164","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":8},{"symbol":"A61K31/4184","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":9},{"symbol":"A61K31/4192","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":10},{"symbol":"A61K31/4196","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":11},{"symbol":"A61K31/42","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":12},{"symbol":"A61K31/422","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":13},{"symbol":"A61K31/426","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":14},{"symbol":"A61K31/437","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":15},{"symbol":"A61K31/4406","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":16},{"symbol":"A61K31/4436","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":17},{"symbol":"A61K31/505","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":18},{"symbol":"A61K31/535","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2006-08-22","class_status":"B","class_data_source":"H","generating_office":"US","sequence":19},{"symbol":"A61K31/5377","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":20},{"symbol":"A61P1/00","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":21},{"symbol":"A61P3/10","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":22},{"symbol":"A61P9/08","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":23},{"symbol":"A61P9/10","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":24},{"symbol":"A61P11/00","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":25},{"symbol":"A61P11/06","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":26},{"symbol":"A61P11/16","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":27},{"symbol":"A61P13/12","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":28},{"symbol":"A61P17/00","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":29},{"symbol":"A61P17/02","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":30},{"symbol":"A61P17/06","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":31},{"symbol":"A61P19/02","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":32},{"symbol":"A61P27/02","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":33},{"symbol":"A61P27/16","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":34},{"symbol":"A61P29/00","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":35},{"symbol":"A61P37/02","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":36},{"symbol":"A61P37/08","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":37},{"symbol":"A61P43/00","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":38},{"symbol":"C07C45/63","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":39},{"symbol":"C07C47/575","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":40},{"symbol":"C07D207/32","version_indicator":"2006-01-01","class_value":"A","action_date":"2008-05-31","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":41},{"symbol":"C07D207/333","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":42},{"symbol":"C07D209/12","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":43},{"symbol":"C07D213/30","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":44},{"symbol":"C07D213/50","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":45},{"symbol":"C07D231/12","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":46},{"symbol":"C07D233/54","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":47},{"symbol":"C07D233/64","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":48},{"symbol":"C07D235/18","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":49},{"symbol":"C07D239/26","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":50},{"symbol":"C07D239/34","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":51},{"symbol":"C07D239/52","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":52},{"symbol":"C07D241/12","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":53},{"symbol":"C07D249/08","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":54},{"symbol":"C07D257/04","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":55},{"symbol":"C07D261/08","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":56},{"symbol":"C07D277/24","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":57},{"symbol":"C07D307/28","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":58},{"symbol":"C07D307/46","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":59},{"symbol":"C07D307/80","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":60},{"symbol":"C07D333/12","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":61},{"symbol":"C07D333/16","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":62},{"symbol":"C07D333/20","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":63},{"symbol":"C07D333/22","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":64},{"symbol":"C07D333/38","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":65},{"symbol":"C07D333/40","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2005-12-20","class_status":"R","class_data_source":"M","generating_office":"JP","sequence":66},{"symbol":"C07D333/56","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2006-08-22","class_status":"B","class_data_source":"H","generating_office":"US","sequence":67},{"symbol":"C07D409/00","version_indicator":"2006-01-01","class_symbol_position":"L","class_value":"I","action_date":"2006-08-22","class_status":"B","class_data_source":"H","generating_office":"US","sequence":68},{"symbol":"C07D409/10","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":69},{"symbol":"C07D409/12","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":70},{"symbol":"C07D413/12","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":71},{"symbol":"C07D471/04","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":72},{"symbol":"C07H15/203","version_indicator":"2006-01-01","class_value":"I","action_date":"2005-10-08","class_status":"R","class_data_source":"M","generating_office":"EP","sequence":73}],"class_ipcr.first_symbol":"A61K31/38","class_ipcr.later_symbol":["A61K31/341","A61K31/381","A61K31/40","A61K31/4025","A61K31/404","A61K31/41","A61K31/4164","A61K31/4184","A61K31/4192","A61K31/4196","A61K31/42","A61K31/422","A61K31/426","A61K31/437","A61K31/4406","A61K31/4436","A61K31/505","A61K31/535","A61K31/5377","A61P1/00","A61P3/10","A61P9/08","A61P9/10","A61P11/00","A61P11/06","A61P11/16","A61P13/12","A61P17/00","A61P17/02","A61P17/06","A61P19/02","A61P27/02","A61P27/16","A61P29/00","A61P37/02","A61P37/08","A61P43/00","C07C45/63","C07C47/575","C07D207/32","C07D207/333","C07D209/12","C07D213/30","C07D213/50","C07D231/12","C07D233/54","C07D233/64","C07D235/18","C07D239/26","C07D239/34","C07D239/52","C07D241/12","C07D249/08","C07D257/04","C07D261/08","C07D277/24","C07D307/28","C07D307/46","C07D307/80","C07D333/12","C07D333/16","C07D333/20","C07D333/22","C07D333/38","C07D333/40","C07D333/56","C07D409/00","C07D409/10","C07D409/12","C07D413/12","C07D471/04","C07H15/203"],"class_ipcr.inv_symbol":["A61K31/38","A61K31/341","A61K31/381","A61K31/40","A61K31/4025","A61K31/404","A61K31/41","A61K31/4164","A61K31/4184","A61K31/4192","A61K31/4196","A61K31/42","A61K31/422","A61K31/426","A61K31/437","A61K31/4406","A61K31/4436","A61K31/505","A61K31/535","A61K31/5377","A61P1/00","A61P3/10","A61P9/08","A61P9/10","A61P11/00","A61P11/06","A61P11/16","A61P13/12","A61P17/00","A61P17/02","A61P17/06","A61P19/02","A61P27/02","A61P27/16","A61P29/00","A61P37/02","A61P37/08","A61P43/00","C07C45/63","C07C47/575","C07D207/333","C07D209/12","C07D213/30","C07D213/50","C07D231/12","C07D233/54","C07D233/64","C07D235/18","C07D239/26","C07D239/34","C07D239/52","C07D241/12","C07D249/08","C07D257/04","C07D261/08","C07D277/24","C07D307/28","C07D307/46","C07D307/80","C07D333/12","C07D333/16","C07D333/20","C07D333/22","C07D333/38","C07D333/40","C07D333/56","C07D409/00","C07D409/10","C07D409/12","C07D413/12","C07D471/04","C07H15/203"],"class_ipcr.add_symbol":["C07D207/32"],"class_ipcr.source":"DOCDB","class_cpc":[{"symbol":"C07C45/63","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":1},{"symbol":"C07C47/575","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":2},{"symbol":"C07D207/333","version_indicator":"2013-01-01","class_symbol_position":"F","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":3},{"symbol":"C07D209/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":4},{"symbol":"C07D213/50","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":5},{"symbol":"C07D231/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":6},{"symbol":"C07D233/64","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":7},{"symbol":"C07D235/18","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":8},{"symbol":"C07D239/26","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":9},{"symbol":"C07D239/52","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":10},{"symbol":"C07D241/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":11},{"symbol":"C07D249/08","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":12},{"symbol":"C07D257/04","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":13},{"symbol":"C07D261/08","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":14},{"symbol":"C07D277/24","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":15},{"symbol":"C07D307/28","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":16},{"symbol":"C07D307/46","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":17},{"symbol":"C07D307/80","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":18},{"symbol":"C07D333/22","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":19},{"symbol":"C07D333/38","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":20},{"symbol":"C07D333/56","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":21},{"symbol":"C07D409/10","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":22},{"symbol":"C07D409/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":23},{"symbol":"C07D413/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":24},{"symbol":"C07D471/04","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":25},{"symbol":"C07H15/203","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":26},{"symbol":"A61P1/00","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-18","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":27},{"symbol":"A61P11/00","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-18","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":28},{"symbol":"A61P11/06","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-18","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":29},{"symbol":"A61P11/16","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-19","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":30},{"symbol":"A61P13/12","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-19","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":31},{"symbol":"A61P17/00","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-19","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":32},{"symbol":"A61P17/02","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-19","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":33},{"symbol":"A61P17/06","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-20","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":34},{"symbol":"A61P19/02","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-20","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":35},{"symbol":"A61P27/02","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-24","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":36},{"symbol":"A61P27/16","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-24","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":37},{"symbol":"A61P29/00","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-25","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":38},{"symbol":"A61P37/02","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-31","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":39},{"symbol":"A61P37/08","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-31","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":40},{"symbol":"A61P43/00","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-31","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":41},{"symbol":"A61P9/00","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-31","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":42},{"symbol":"A61P9/08","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-31","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":43},{"symbol":"A61P9/10","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-31","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":44},{"symbol":"A61P3/10","version_indicator":"2018-01-01","class_symbol_position":"L","class_value":"I","action_date":"2020-03-31","class_status":"B","class_data_source":"H","generating_office":"EP","sequence":45},{"symbol":"C07D207/333","version_indicator":"2013-01-01","class_symbol_position":"F","class_value":"I","action_date":"2019-08-22","class_status":"B","class_data_source":"H","generating_office":"US","sequence":47},{"symbol":"C07C47/575","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":48},{"symbol":"C07D307/28","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":49},{"symbol":"C07D209/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":50},{"symbol":"C07D409/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":51},{"symbol":"C07D257/04","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":52},{"symbol":"C07D241/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":53},{"symbol":"C07D213/50","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":54},{"symbol":"C07D307/80","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":55},{"symbol":"C07D333/22","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":56},{"symbol":"C07D233/64","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":57},{"symbol":"C07D413/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":58},{"symbol":"C07D333/56","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":59},{"symbol":"C07D333/38","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":60},{"symbol":"C07D239/52","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":61},{"symbol":"C07D261/08","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":62},{"symbol":"C07D471/04","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":63},{"symbol":"C07D235/18","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":64},{"symbol":"C07D239/26","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":65},{"symbol":"C07H15/203","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":66},{"symbol":"C07C45/63","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":67},{"symbol":"C07D307/46","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":68},{"symbol":"C07D277/24","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":69},{"symbol":"C07D249/08","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":70},{"symbol":"C07D409/10","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":71},{"symbol":"C07D231/12","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US","sequence":72}],"class_cpc_cset":[{"class":[{"symbol":"C07C45/63","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP"},{"symbol":"C07C47/575","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2013-01-01","class_status":"B","class_data_source":"H","generating_office":"EP"}],"sequence":46},{"class":[{"symbol":"C07C45/63","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US"},{"symbol":"C07C47/575","version_indicator":"2013-01-01","class_symbol_position":"L","class_value":"I","action_date":"2019-10-11","class_status":"B","class_data_source":"H","generating_office":"US"}],"sequence":73}],"class_cpc.first_symbol":"C07D207/333","class_cpc.later_symbol":["C07C45/63","C07C47/575","C07D209/12","C07D213/50","C07D231/12","C07D233/64","C07D235/18","C07D239/26","C07D239/52","C07D241/12","C07D249/08","C07D257/04","C07D261/08","C07D277/24","C07D307/28","C07D307/46","C07D307/80","C07D333/22","C07D333/38","C07D333/56","C07D409/10","C07D409/12","C07D413/12","C07D471/04","C07H15/203","A61P1/00","A61P11/00","A61P11/06","A61P11/16","A61P13/12","A61P17/00","A61P17/02","A61P17/06","A61P19/02","A61P27/02","A61P27/16","A61P29/00","A61P37/02","A61P37/08","A61P43/00","A61P9/00","A61P9/08","A61P9/10","A61P3/10","C07C47/575","C07D307/28","C07D209/12","C07D409/12","C07D257/04","C07D241/12","C07D213/50","C07D307/80","C07D333/22","C07D233/64","C07D413/12","C07D333/56","C07D333/38","C07D239/52","C07D261/08","C07D471/04","C07D235/18","C07D239/26","C07H15/203","C07C45/63","C07D307/46","C07D277/24","C07D249/08","C07D409/10","C07D231/12"],"class_cpc.inv_symbol":["C07C45/63","C07C47/575","C07D207/333","C07D209/12","C07D213/50","C07D231/12","C07D233/64","C07D235/18","C07D239/26","C07D239/52","C07D241/12","C07D249/08","C07D257/04","C07D261/08","C07D277/24","C07D307/28","C07D307/46","C07D307/80","C07D333/22","C07D333/38","C07D333/56","C07D409/10","C07D409/12","C07D413/12","C07D471/04","C07H15/203","A61P1/00","A61P11/00","A61P11/06","A61P11/16","A61P13/12","A61P17/00","A61P17/02","A61P17/06","A61P19/02","A61P27/02","A61P27/16","A61P29/00","A61P37/02","A61P37/08","A61P43/00","A61P9/00","A61P9/08","A61P9/10","A61P3/10","C07D207/333","C07C47/575","C07D307/28","C07D209/12","C07D409/12","C07D257/04","C07D241/12","C07D213/50","C07D307/80","C07D333/22","C07D233/64","C07D413/12","C07D333/56","C07D333/38","C07D239/52","C07D261/08","C07D471/04","C07D235/18","C07D239/26","C07H15/203","C07C45/63","C07D307/46","C07D277/24","C07D249/08","C07D409/10","C07D231/12"],"class_cpc.add_symbol":[],"class_cpc.source":"DOCDB","class_national":[{"symbol":"514/443","symbol_position":"F"},{"symbol":"514/422","symbol_position":"L"},{"symbol":"514/231.5","symbol_position":"L"},{"symbol":"548/527","symbol_position":"L"},{"symbol":"549/58","symbol_position":"L"},{"symbol":"544/146","symbol_position":"L"}],"class_national.first_symbol":"514/443","class_national.later_symbol":["514/422","514/231.5","548/527","549/58","544/146"],"class_national.source":"DOCDB","reference_cited":[{"patent":{"num":1,"document_id":{"jurisdiction":"US","doc_number":"4698291","kind":"A","date":"1987-10-06","name":"KOIBUCHI SHIGERU [JP], et al"},"lens_id":"037-988-497-541-932","category":[],"us_category":[],"cited_phase":"SEA","rel_claims":[],"sequence":1}},{"patent":{"num":2,"document_id":{"jurisdiction":"US","doc_number":"5068364","kind":"A","date":"1991-11-26","name":"TAKAGAKI HIDETSUGU [JP], et al"},"lens_id":"115-508-327-080-303","category":[],"us_category":[],"cited_phase":"SEA","rel_claims":[],"sequence":2}},{"patent":{"num":3,"document_id":{"jurisdiction":"US","doc_number":"6677350","kind":"B1","date":"2004-01-13","name":"LIN YUH-MEEI [US]"},"lens_id":"170-467-407-618-413","category":[],"us_category":[],"cited_phase":"SEA","rel_claims":[],"sequence":3}},{"patent":{"num":1,"document_id":{"jurisdiction":"US","doc_number":"3862176","kind":"A","date":"1975-01-21","name":"FAURAN CLAUDE P, et al"},"lens_id":"192-660-944-987-436","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":1}},{"patent":{"num":2,"document_id":{"jurisdiction":"US","doc_number":"4085135","kind":"A","date":"1978-04-18","name":"KYOGOKU KAZUAKI, et al"},"lens_id":"092-916-781-212-927","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":2}},{"patent":{"num":3,"document_id":{"jurisdiction":"US","doc_number":"4522811","kind":"A","date":"1985-06-11","name":"EPPSTEIN DEBORAH A [US], et al"},"lens_id":"122-154-948-208-611","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":3}},{"patent":{"num":4,"document_id":{"jurisdiction":"US","doc_number":"4855438","kind":"A","date":"1989-08-08","name":"KAULEN JOHANNES [DE], et al"},"lens_id":"122-451-932-973-539","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":4}},{"patent":{"num":5,"document_id":{"jurisdiction":"US","doc_number":"4904697","kind":"A","date":"1990-02-27","name":"SUNKARA SAI P [US], et al"},"lens_id":"131-218-918-084-503","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":5}},{"patent":{"num":6,"document_id":{"jurisdiction":"US","doc_number":"5155250","kind":"A","date":"1992-10-13","name":"PARKER ROGER A [US], et al"},"lens_id":"045-172-918-641-893","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":6}},{"patent":{"num":7,"document_id":{"jurisdiction":"US","doc_number":"5217999","kind":"A","date":"1993-06-08","name":"LEVITZKI ALEXANDER [IL], et al"},"lens_id":"178-901-599-640-518","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":7}},{"patent":{"num":8,"document_id":{"jurisdiction":"US","doc_number":"5380747","kind":"A","date":"1995-01-10","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"045-248-246-431-161","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":8}},{"patent":{"num":9,"document_id":{"jurisdiction":"US","doc_number":"5608095","kind":"A","date":"1997-03-04","name":"PARKER ROGER A [US], et al"},"lens_id":"045-285-132-909-166","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":9}},{"patent":{"num":10,"document_id":{"jurisdiction":"US","doc_number":"5631365","kind":"A","date":"1997-05-20","name":"ROSENBLUM STUART B [US]"},"lens_id":"166-259-422-237-714","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":10}},{"patent":{"num":11,"document_id":{"jurisdiction":"US","doc_number":"5744614","kind":"A","date":"1998-04-28","name":"MERKLE HANS RUPERT [DE], et al"},"lens_id":"088-666-624-038-167","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":11}},{"patent":{"num":12,"document_id":{"jurisdiction":"US","doc_number":"5750351","kind":"A","date":"1998-05-12","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"158-766-804-184-183","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":12}},{"patent":{"num":13,"document_id":{"jurisdiction":"US","doc_number":"5767115","kind":"A","date":"1998-06-16","name":"ROSENBLUM STUART B [US], et al"},"lens_id":"110-600-246-223-384","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":13}},{"patent":{"num":14,"document_id":{"jurisdiction":"US","doc_number":"5773209","kind":"A","date":"1998-06-30","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"056-939-674-324-647","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":14}},{"patent":{"num":15,"document_id":{"jurisdiction":"US","doc_number":"5773231","kind":"A","date":"1998-06-30","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"089-352-600-348-843","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":15}},{"patent":{"num":16,"document_id":{"jurisdiction":"US","doc_number":"5783596","kind":"A","date":"1998-07-21","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"089-501-118-590-70X","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":16}},{"patent":{"num":17,"document_id":{"jurisdiction":"US","doc_number":"5786355","kind":"A","date":"1998-07-28","name":"KONNO YASUO [JP], et al"},"lens_id":"083-306-229-015-079","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":17}},{"patent":{"num":18,"document_id":{"jurisdiction":"US","doc_number":"5792787","kind":"A","date":"1998-08-11","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"096-612-859-261-001","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":18}},{"patent":{"num":19,"document_id":{"jurisdiction":"US","doc_number":"5807884","kind":"A","date":"1998-09-15","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"013-037-694-986-83X","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":19}},{"patent":{"num":20,"document_id":{"jurisdiction":"US","doc_number":"5808137","kind":"A","date":"1998-09-15","name":"BOMBARDELLI EZIO [IT], et al"},"lens_id":"147-198-463-767-097","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":20}},{"patent":{"num":21,"document_id":{"jurisdiction":"US","doc_number":"5811449","kind":"A","date":"1998-09-22","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"101-966-086-324-468","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":21}},{"patent":{"num":22,"document_id":{"jurisdiction":"US","doc_number":"5821260","kind":"A","date":"1998-10-13","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"143-110-149-999-629","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":22}},{"patent":{"num":23,"document_id":{"jurisdiction":"US","doc_number":"5846959","kind":"A","date":"1998-12-08","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"154-541-274-197-821","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":23}},{"patent":{"num":24,"document_id":{"jurisdiction":"US","doc_number":"5877203","kind":"A","date":"1999-03-02","name":"MEDFORD RUSSELL M [US], et al"},"lens_id":"189-823-915-711-305","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":24}},{"patent":{"num":25,"document_id":{"jurisdiction":"US","doc_number":"5951841","kind":"A","date":"1999-09-14","name":"WEHLAGE THOMAS [DE], et al"},"lens_id":"014-407-989-896-980","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":25}},{"patent":{"num":26,"document_id":{"jurisdiction":"US","doc_number":"6046212","kind":"A","date":"2000-04-04","name":"ZWAAGSTRA MARIA ELIZABETH [NL], et al"},"lens_id":"113-181-331-214-939","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":26}},{"patent":{"num":27,"document_id":{"jurisdiction":"US","doc_number":"6069148","kind":"A","date":"2000-05-30","name":"SCHMIDT GUNTER [DE], et al"},"lens_id":"050-164-596-986-194","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":27}},{"patent":{"num":28,"document_id":{"jurisdiction":"US","doc_number":"6140343","kind":"A","date":"2000-10-31","name":"DENINNO MICHAEL P [US], et al"},"lens_id":"198-662-852-182-136","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":28}},{"patent":{"num":29,"document_id":{"jurisdiction":"US","doc_number":"6147089","kind":"A","date":"2000-11-14","name":"DENINNO MICHAEL P [US], et al"},"lens_id":"023-088-116-803-272","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":29}},{"patent":{"num":30,"document_id":{"jurisdiction":"US","doc_number":"6147090","kind":"A","date":"2000-11-14","name":"DENINNO MICHAEL P [US], et al"},"lens_id":"168-550-662-148-282","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":30}},{"patent":{"num":31,"document_id":{"jurisdiction":"US","doc_number":"6159988","kind":"A","date":"2000-12-12","name":"NAIK RAMACHANDRA GANAPATI [IN], et al"},"lens_id":"021-038-006-045-425","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":31}},{"patent":{"num":32,"document_id":{"jurisdiction":"US","doc_number":"6162445","kind":"A","date":"2000-12-19","name":"BERNARDON JEAN-MICHEL [FR]"},"lens_id":"070-539-263-494-806","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":32}},{"patent":{"num":33,"document_id":{"jurisdiction":"US","doc_number":"6197786","kind":"B1","date":"2001-03-06","name":"DENINNO MICHAEL P [US], et al"},"lens_id":"073-691-007-881-415","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":33}},{"patent":{"num":34,"document_id":{"jurisdiction":"US","doc_number":"6310075","kind":"B1","date":"2001-10-30","name":"DENINNO MICHAEL P [US], et al"},"lens_id":"010-064-747-480-90X","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":34}},{"patent":{"num":35,"document_id":{"jurisdiction":"US","doc_number":"6313142","kind":"B1","date":"2001-11-06","name":"DAMON DAVID B [US], et al"},"lens_id":"075-275-906-652-878","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":35}},{"patent":{"num":36,"document_id":{"jurisdiction":"US","doc_number":"6423740","kind":"B1","date":"2002-07-23","name":"BOMBARDELLI EZIO [IT], et al"},"lens_id":"132-392-536-193-405","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":36}},{"patent":{"num":37,"document_id":{"jurisdiction":"US","doc_number":"6462075","kind":"B1","date":"2002-10-08","name":"BOWEN J PHILLIP [US], et al"},"lens_id":"118-530-001-925-695","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":37}},{"patent":{"num":38,"document_id":{"jurisdiction":"US","doc_number":"6608101","kind":"B1","date":"2003-08-19","name":"NI LIMING [US], et al"},"lens_id":"021-603-533-766-290","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":38}},{"patent":{"num":39,"document_id":{"jurisdiction":"US","doc_number":"2003232877","kind":"A1","date":"2003-12-18","name":"SIKORSKI JAMES A [US], et al"},"lens_id":"143-016-931-632-367","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":39}},{"patent":{"num":40,"document_id":{"jurisdiction":"US","doc_number":"2003236298","kind":"A1","date":"2003-12-25","name":"MENG CHARLES Q [US], et al"},"lens_id":"046-265-841-608-989","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":40}},{"patent":{"num":41,"document_id":{"jurisdiction":"US","doc_number":"2004048858","kind":"A1","date":"2004-03-11","name":"SIKORSKI JAMES A [US], et al"},"lens_id":"188-431-610-237-076","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":41}},{"patent":{"num":42,"document_id":{"jurisdiction":"EP","doc_number":"0307762","kind":"A1","date":"1989-03-22","name":"HOFFMANN LA ROCHE [CH]"},"lens_id":"178-571-215-707-842","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":42}},{"patent":{"num":43,"document_id":{"jurisdiction":"EP","doc_number":"0271307","kind":"A2","date":"1988-06-15","name":"HOECHST CELANESE CORP [US]"},"lens_id":"095-716-734-149-868","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":43}},{"patent":{"num":44,"document_id":{"jurisdiction":"EP","doc_number":"0476658","kind":"A1","date":"1992-03-25","name":"MERRELL DOW PHARMA [US]"},"lens_id":"199-621-481-185-463","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":44}},{"patent":{"num":45,"document_id":{"jurisdiction":"FR","doc_number":"2175634","kind":"A1","date":"1973-10-26","name":"DELALANDE SA [FR]"},"lens_id":"115-134-389-079-507","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":45}},{"patent":{"num":46,"document_id":{"jurisdiction":"GB","doc_number":"1408754","kind":"A","date":"1975-10-01","name":"DELALANDE SA"},"lens_id":"005-242-261-695-757","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":46}},{"patent":{"num":47,"document_id":{"jurisdiction":"JP","doc_number":"S6310720","kind":"A","date":"1988-01-18","name":"NIPPON KAYAKU KK"},"lens_id":"129-232-533-243-795","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":47}},{"patent":{"num":48,"document_id":{"jurisdiction":"JP","doc_number":"H04217621","kind":"A","date":"1992-08-07","name":"SHISEIDO CO LTD"},"lens_id":"116-270-970-146-120","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":48}},{"patent":{"num":49,"document_id":{"jurisdiction":"JP","doc_number":"H0692950","kind":"A","date":"1994-04-05","name":"KANEGAFUCHI CHEMICAL IND"},"lens_id":"124-781-540-216-242","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":49}},{"patent":{"num":50,"document_id":{"jurisdiction":"JP","doc_number":"H06116206","kind":"A","date":"1994-04-26","name":"MORINAGA MILK INDUSTRY CO LTD"},"lens_id":"156-907-361-124-854","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":50}},{"patent":{"num":51,"document_id":{"jurisdiction":"JP","doc_number":"H07330814","kind":"A","date":"1995-12-19","name":"HITACHI CHEMICAL CO LTD"},"lens_id":"081-289-508-376-489","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":51}},{"patent":{"num":52,"document_id":{"jurisdiction":"WO","doc_number":"9515760","kind":"A1","date":"1995-06-15","name":"MERRELL DOW PHARMA [US], et al"},"lens_id":"010-732-946-255-511","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":52}},{"patent":{"num":53,"document_id":{"jurisdiction":"WO","doc_number":"9608484","kind":"A1","date":"1996-03-21","name":"MONSANTO CO [US], et al"},"lens_id":"135-713-982-601-521","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":53}},{"patent":{"num":54,"document_id":{"jurisdiction":"WO","doc_number":"9620936","kind":"A1","date":"1996-07-11","name":"SUNKYONG IND LTD [KR], et al"},"lens_id":"078-511-844-276-440","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":54}},{"patent":{"num":55,"document_id":{"jurisdiction":"WO","doc_number":"9712613","kind":"A1","date":"1997-04-10","name":"WARNER LAMBERT CO [US], et al"},"lens_id":"021-628-371-310-610","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":55}},{"patent":{"num":56,"document_id":{"jurisdiction":"WO","doc_number":"9733882","kind":"A1","date":"1997-09-18","name":"SEARLE & CO [US], et al"},"lens_id":"061-030-677-899-637","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":56}},{"patent":{"num":57,"document_id":{"jurisdiction":"WO","doc_number":"9804528","kind":"A2","date":"1998-02-05","name":"BAYER AG [US], et al"},"lens_id":"086-910-257-933-491","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":57}},{"patent":{"num":58,"document_id":{"jurisdiction":"WO","doc_number":"9823581","kind":"A1","date":"1998-06-04","name":"BASF AG [DE], et al"},"lens_id":"157-776-536-213-365","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":58}},{"patent":{"num":59,"document_id":{"jurisdiction":"WO","doc_number":"9823581","kind":"A1","date":"1998-06-04","name":"BASF AG [DE], et al"},"lens_id":"157-776-536-213-365","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":59}},{"patent":{"num":60,"document_id":{"jurisdiction":"WO","doc_number":"9835937","kind":"A1","date":"1998-08-20","name":"JAPAN TOBACCO INC [JP], et al"},"lens_id":"165-108-963-353-166","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":60}},{"patent":{"num":61,"document_id":{"jurisdiction":"WO","doc_number":"9840375","kind":"A2","date":"1998-09-17","name":"SEARLE & CO [US], et al"},"lens_id":"065-066-494-478-573","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":61}},{"patent":{"num":62,"document_id":{"jurisdiction":"WO","doc_number":"9851289","kind":"A2","date":"1998-11-19","name":"ATHEROGENICS INC [US], et al"},"lens_id":"138-067-863-493-850","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":62}},{"patent":{"num":63,"document_id":{"jurisdiction":"WO","doc_number":"9851662","kind":"A2","date":"1998-11-19","name":"ATHEROGENICS INC [US], et al"},"lens_id":"173-085-850-629-075","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":63}},{"patent":{"num":64,"document_id":{"jurisdiction":"WO","doc_number":"9900114","kind":"A2","date":"1999-01-07","name":"STATENS SERUMINSTITUT [DK], et al"},"lens_id":"014-253-644-251-109","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":64}},{"patent":{"num":65,"document_id":{"jurisdiction":"WO","doc_number":"9900114","kind":"A2","date":"1999-01-07","name":"STATENS SERUMINSTITUT [DK], et al"},"lens_id":"014-253-644-251-109","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":65}},{"patent":{"num":66,"document_id":{"jurisdiction":"WO","doc_number":"9914174","kind":"A1","date":"1999-03-25","name":"BAYER AG [DE], et al"},"lens_id":"004-884-974-596-650","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":66}},{"patent":{"num":67,"document_id":{"jurisdiction":"WO","doc_number":"9914215","kind":"A1","date":"1999-03-25","name":"BAYER AG [DE], et al"},"lens_id":"115-776-111-272-382","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":67}},{"patent":{"num":68,"document_id":{"jurisdiction":"WO","doc_number":"9915504","kind":"A1","date":"1999-04-01","name":"BAYER AG [DE], et al"},"lens_id":"195-907-575-601-518","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":68}},{"patent":{"num":69,"document_id":{"jurisdiction":"WO","doc_number":"0018721","kind":"A1","date":"2000-04-06","name":"MONSANTO CO [US], et al"},"lens_id":"184-734-711-341-73X","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":69}},{"patent":{"num":70,"document_id":{"jurisdiction":"WO","doc_number":"0018723","kind":"A1","date":"2000-04-06","name":"MONSANTO CO [US], et al"},"lens_id":"006-270-033-292-897","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":70}},{"patent":{"num":71,"document_id":{"jurisdiction":"WO","doc_number":"0018724","kind":"A1","date":"2000-04-06","name":"MONSANTO CO [US], et al"},"lens_id":"132-651-382-145-139","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":71}},{"patent":{"num":72,"document_id":{"jurisdiction":"WO","doc_number":"0038725","kind":"A1","date":"2000-07-06","name":"SEARLE & CO [US], et al"},"lens_id":"193-364-067-274-265","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":72}},{"patent":{"num":73,"document_id":{"jurisdiction":"WO","doc_number":"0047554","kind":"A2","date":"2000-08-17","name":"COR THERAPEUTICS INC [US]"},"lens_id":"114-791-757-319-556","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":73}},{"patent":{"num":74,"document_id":{"jurisdiction":"WO","doc_number":"0017166","kind":"A1","date":"2000-03-30","name":"PFIZER PROD INC [US], et al"},"lens_id":"080-449-288-862-55X","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":74}},{"patent":{"num":75,"document_id":{"jurisdiction":"WO","doc_number":"2004056727","kind":"A2","date":"2004-07-08","name":"ATHEROGENICS INC [US], et al"},"lens_id":"045-995-540-557-91X","category":[],"us_category":[],"cited_phase":"APP","rel_claims":[],"sequence":75}},{"npl":{"num":1,"text":"Liu et al., Antimalarial Alkoxylated and Hydroxylated Chalones: Structure-Activity Relationship Analysis, J. Med. Chem. 2001, 44, 4443-4452.","npl_type":"a","external_id":["11728189","10.1021/jm0101747"],"record_lens_id":"002-911-160-091-424","lens_id":["193-985-918-365-352","002-911-160-091-424","014-288-956-078-691"],"sequence":76,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":2,"text":"Herencia et al, Novel Anti-inflammatory Chalcone Derivatives Inhibit the Induction of Nitric Oxide Synthase and Cyclooxygenase-2 in Mouse Peritoneal Macrophages, FEBS Letters, 1999, 453, 129-134.","npl_type":"a","external_id":["10.1016/s0014-5793(99)00707-3","10403389"],"record_lens_id":"032-235-674-646-690","lens_id":["137-225-668-681-367","032-235-674-646-690","120-935-845-348-215"],"sequence":77,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":3,"text":"Herencia, et al., in Synthesis and Anti-inflammatory Activity of Chalcone Derivatives, Bioorganic & Medicinal Chemistry Letters 8 (1998) 1169-1174.","npl_type":"a","external_id":["9871729","10.1016/s0960-894x(98)00179-6"],"record_lens_id":"013-002-699-678-051","lens_id":["114-137-025-718-264","013-002-699-678-051","127-072-855-403-71X"],"sequence":78,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":4,"text":"Hsieh et al., Synthesis and Anti-inflammatory Effect of Chalcones and Related Compounds, Pharmaceutical Research, 1998, vol. 15, No. 1, 39-46.","npl_type":"a","external_id":["10.1023/a:1011940401754","9487544"],"record_lens_id":"059-624-620-380-013","lens_id":["128-502-375-736-922","059-624-620-380-013","135-465-001-186-616"],"sequence":79,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":5,"text":"Hsieh, et al., Synthesis and Anti-inflammatory Effect of Chalcones, J. Pharm. Pharmacol. 2000, 52; 163-171..","npl_type":"a","external_id":["10714946","10.1211/0022357001773814"],"record_lens_id":"005-684-578-639-540","lens_id":["015-458-999-873-930","005-684-578-639-540","100-597-032-075-024"],"sequence":80,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":6,"text":"Jones R. and N. Bischofberger, Antiviral Research, 27 (1995) 1-17.","npl_type":"a","external_id":["7486948","10.1016/0166-3542(95)00011-a"],"record_lens_id":"006-356-668-723-66X","lens_id":["092-129-737-480-841","006-356-668-723-66X","173-045-669-079-412"],"sequence":81,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":7,"text":"Yang, Y., et al., Heterocycles, 1992, 34(6), 1169-1175.","npl_type":"a","external_id":["10.3987/com-92-6009"],"record_lens_id":"040-174-626-813-638","lens_id":["085-933-825-861-621","040-174-626-813-638"],"sequence":82,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":8,"text":"Zwaagstra, et al., Synthesis and Structure-Activity Relationships of Carboxylated Chalcones: A Novel Series of CysLT1 (LT4) Receptor Antagonists; J. Med. Chem., 1997, 40, 1075-1089.","npl_type":"a","external_id":["10.1021/jm960628d","9089329"],"record_lens_id":"029-705-891-232-799","lens_id":["058-957-883-766-953","029-705-891-232-799","059-662-975-619-641"],"sequence":83,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":9,"text":"Abraham, W., et al., \"Blockade of Late-phase Airway Reponses and Airway Hyperresponsiveness in Allergic Sheep with a Small-molecule Peptide Inhibitor of VLA-4,\" Am. J. Respir. Crit. Care Med., 156:696-703 (1997),.","npl_type":"a","external_id":["10.1164/ajrccm.156.3.9609039","9309981"],"record_lens_id":"053-629-007-161-634","lens_id":["168-510-588-501-730","053-629-007-161-634","198-654-525-898-612"],"sequence":84,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":10,"text":"Albertini, J.P., et al., \"Increase in Serum Levels of Adhesion Glycoprpteins in NIDDM Effect of Intensive Insulin Treatment,\" Diabetologia, 39:A240 (1996).","npl_type":"a","external_id":[],"lens_id":[],"sequence":85,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":11,"text":"Bakhite, E. A., et al., \"Synthesis and application of some new oxazole derivatives as antimicrobial agents,\" J. Chem. Tech. Biotech., 55:157-161 (1992).","npl_type":"a","external_id":[],"lens_id":[],"sequence":86,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":12,"text":"Baraczka, K., et al., \"A Study Of Increased Levels Of Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) In The Cerebrospinal Fluid of Patients With Multiple Sclerosis And systemic Lupus Erythematosus,\" Acta. Neurol. Scand., 99:95-99 (1999).","npl_type":"a","external_id":["10071167","10.1111/j.1600-0404.1999.tb00664.x"],"record_lens_id":"082-153-747-794-112","lens_id":["125-045-418-574-864","082-153-747-794-112","127-820-054-329-59X"],"sequence":87,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":13,"text":"Belmont, H.M., et. al., \"Up-Regulation of Endothelial Cell Adhesion Molecules Characterizes Disease Activity in Systemic Lupus Erythematosus,\" Arthritis & Rheumatism, 37(3):376-383 (1994).","npl_type":"a","external_id":["10.1002/art.1780370311","7510492"],"record_lens_id":"040-272-616-986-286","lens_id":["187-299-720-611-59X","040-272-616-986-286","126-717-002-648-722"],"sequence":88,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":14,"text":"Boratynska, M., et al., :Soluble cell adhesion molecules in chronic renal graft rejection, Pol. Arch. Med. Wewn, 100:410-418 (1998).","npl_type":"a","external_id":["10410574"],"record_lens_id":"139-119-123-751-955","lens_id":["161-651-231-672-953","139-119-123-751-955"],"sequence":89,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":15,"text":"Bousquet, J., et. al., \"Eosinophilic Inflammation in Asthma\" N. Engl. J. Med., 323(15):1033-1039 (1990).","npl_type":"a","external_id":["2215562","10.1056/nejm199010113231505"],"record_lens_id":"006-219-983-634-375","lens_id":["065-228-317-009-302","006-219-983-634-375","015-870-363-030-22X"],"sequence":90,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":16,"text":"Braunstahl,G.J., et. al., \"Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways,\" J. Allergy Clin. Immunol., 107:469-476 (2001).","npl_type":"a","external_id":["10.1067/mai.2001.113046","11240947"],"record_lens_id":"028-182-957-369-530","lens_id":["063-769-263-315-046","028-182-957-369-530","088-331-075-737-04X"],"sequence":91,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":17,"text":"Calliste, C.-A., et al., \"Chalcones: Structural Requirements for Antioxidant, Estrogenic and Antiproliferative Activities,\" Anticancer Research, 21:3949-3956 (2001).","npl_type":"a","external_id":["11911276"],"record_lens_id":"069-727-897-204-914","lens_id":["118-648-357-690-261","069-727-897-204-914"],"sequence":92,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":18,"text":"Cheng, Z.-J., et al., \"Broussochalcone A, a potent antioxidant and effective suppressor of inducible nitric oxide synthase in lipoplysaccharide-activated macrophages,\" Biochemical Pharmacology, 61:939-946 (2001).","npl_type":"a","external_id":["11286985","10.1016/s0006-2952(01)00543-3"],"record_lens_id":"029-464-770-301-650","lens_id":["040-561-733-977-750","029-464-770-301-650","196-470-323-965-769"],"sequence":93,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":19,"text":"Corey, E.J., et al., \"A synthetic method for formyl-ethynyl conversion (RCHO->RC-CH or RC-CR1),\" Tetrahedron Letters, 1972(36):3769-3772 (1972).","npl_type":"a","external_id":["10.1016/s0040-4039(01)94157-7"],"record_lens_id":"012-878-244-759-218","lens_id":["055-390-338-714-740","012-878-244-759-218"],"sequence":94,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":20,"text":"Cosimi, A.B., et al., \"In Vivo Effects of Monoclonal Antibody to ICAM-1 (CD54) in Nonhuman Primates with Renal Allografts,\" J. Immunol., 144(12):4604-4612 (1990).","npl_type":"a","external_id":["1972162"],"record_lens_id":"181-422-103-616-822","lens_id":["194-842-796-802-793","181-422-103-616-822"],"sequence":95,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":21,"text":"Dimmock, J.R., et al., \"Cytotoxic Activities of Mannich Bases of Chalcones and Related Compounds,\" J. Med. Chem., 41(7):1014-1026 (1998).","npl_type":"a","external_id":["9544201","10.1021/jm970432t"],"record_lens_id":"129-046-707-491-520","lens_id":["168-277-551-148-250","129-046-707-491-520","193-710-311-197-425"],"sequence":96,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":22,"text":"Dimmock, J.R., et al., \"Bioactivities of chalcones,\" Current Medicinal Chemistry, 6(12):1125-1149 (1999).","npl_type":"a","external_id":["10519918"],"record_lens_id":"042-295-803-549-14X","lens_id":["169-516-541-217-357","042-295-803-549-14X"],"sequence":97,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":23,"text":"Dinkova-Kostova, A.T., et al., \"Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups,\" Proc. Natl. Acad. Sci. U.S.A., 98(6):3404-3409 (Mar. 13, 2001).","npl_type":"a","external_id":["11248091","10.1073/pnas.051632198","pmc30666"],"record_lens_id":"025-544-556-756-683","lens_id":["189-036-076-443-238","025-544-556-756-683","165-345-072-165-566"],"sequence":98,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":24,"text":"Elovaara, I., et al., \"Adhesion Molecules in Multiple Sclerosis,\" Arch. Neurol., 57:546-551 (2000).","npl_type":"a","external_id":["10768630","10.1001/archneur.57.4.546"],"record_lens_id":"015-193-439-999-737","lens_id":["162-945-189-705-140","015-193-439-999-737","067-571-897-772-953"],"sequence":99,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":25,"text":"Endo, A., \"The discovery and development of HMG-CoA reductase inhibitors,\" J. Lipid Res., 33:1569-1582 (1992).","npl_type":"a","external_id":["10.1016/s0022-2275(20)41379-3","1464741"],"record_lens_id":"082-576-335-625-296","lens_id":["101-214-000-580-275","082-576-335-625-296","086-539-993-646-614"],"sequence":100,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":26,"text":"Enghofer, M., et al., \"Vascular Cell Adhesion Molecule 1 Mediates Islet Lymphocyte Adhession in Diabetic Insulitis in Mice,\" Diabetologia, 39:A97 (1996).","npl_type":"a","external_id":[],"lens_id":[],"sequence":101,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":27,"text":"Frigerio, S.,et al., \"Cerebrospinal fluid thrombomodulin and sVCAM-1 in different clinical stages of multiple sclerosis patients,\" Neuroimmunol., 87:88-93 (1998).","npl_type":"a","external_id":["10.1016/s0165-5728(98)00045-9","9670849"],"record_lens_id":"079-495-529-898-599","lens_id":["180-420-838-881-373","079-495-529-898-599","113-715-548-383-091"],"sequence":102,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":28,"text":"Furuzawa-Carballeda, J., et al., \"Interleukin-8, interleukin-10, intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Expression Levels are Higher in Synovial Tissue for Patients with Rheumatoid Arthritis than in Osteoarthritis,\" Scand. J. Immunol., 50:215-222 (1999).","npl_type":"a","external_id":["10447928","10.1046/j.1365-3083.1999.00573.x"],"record_lens_id":"010-138-186-129-800","lens_id":["130-503-242-355-882","010-138-186-129-800","135-949-455-178-312"],"sequence":103,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":29,"text":"Goeke, M.N., et al., \"Elevation of Soluble VCAM-1 in the Serum of Patients with Inflammatory Bowel Disease,\" Gastroenterology, 106:A689 (1994).","npl_type":"a","external_id":[],"lens_id":[],"sequence":104,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":30,"text":"Goggins, M.G., et al., \"Serum VCAM-1 reflects the grade of intestinal inflammation in patients with Crohn's disease,\" Gastroenterology, 108:A825 (1995).","npl_type":"a","external_id":["10.1016/0016-5085(95)27607-6"],"record_lens_id":"035-324-143-335-635","lens_id":["061-358-683-936-851","035-324-143-335-635"],"sequence":105,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":31,"text":"Göke, M., et al., \"Elevated serum concentrations of soluble selectin and immunoglobulin type adhe-sion molecules in patients with inflammatory bowel disease,\" J. Gasterokenterol., 32:480-486 (1997).","npl_type":"a","external_id":["10.1007/bf02934086","9250894"],"record_lens_id":"030-349-485-345-760","lens_id":["124-213-566-269-283","030-349-485-345-760","120-339-728-264-847"],"sequence":106,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":32,"text":"Gordon, F.H., et al., \"Adhesion Molecule Expression in Inflammatory Bowel Disease (IBD) Patients Treated with Natalizumab (Antegrentm), a Humanized Antibody to A2 Integrin,\" Gastroenterology, 118 (No. 4, Suppl 2), A344 (2000).","npl_type":"a","external_id":["10.1016/s0016-5085(00)83477-0"],"record_lens_id":"094-467-853-254-467","lens_id":["097-430-194-807-039","094-467-853-254-467"],"sequence":107,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":33,"text":"Gosset, P., et al., \"Expression of E-Selection, ICAM-1 and VCAM-1 on Bronchial Biopsies from Allergic and Non-Allergic Patients,\" Int. Arch. Allergy Immunol., 106:69-77 (1995).","npl_type":"a","external_id":["10.1159/000236892","7529075"],"record_lens_id":"122-864-327-841-613","lens_id":["190-032-476-407-778","122-864-327-841-613","163-032-754-892-20X"],"sequence":108,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":34,"text":"Groves, R.W., et al., \"Vascular cell adhesion molecule-1: Expression in normal and diseased skin and regulation in vivo by interferon gamma,\" J. Am. Acad. Dermatol., 29:67-72 (1993).","npl_type":"a","external_id":["7686190","10.1016/0190-9622(93)70154-l"],"record_lens_id":"086-475-641-232-119","lens_id":["185-374-425-561-213","086-475-641-232-119","183-177-739-231-65X"],"sequence":109,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":35,"text":"Grünbaum, Z., et al., \"Nucleophilic Attacks on Carbon-Carbon Double Bonds. Part X. Nucleophile-catalysed cis-trans Isomerisation of cis-4-Nitrochalcone and of Diethyl Maleate in 95% Ethanol,\" J. Chem. Soc. (B), 1966:1133-1137 (1966).","npl_type":"a","external_id":["10.1039/j29660001133"],"record_lens_id":"005-955-616-985-148","lens_id":["174-898-282-201-12X","005-955-616-985-148"],"sequence":110,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":36,"text":"Grundy, S.M., \"HMG-CoA Reductase inhibitors for treatment of hypercholesterolemia,\" New Engl. J. Med., 319:24-33 (Jul. 7, 1988).","npl_type":"a","external_id":["10.1056/nejm198807073190105","3288867"],"record_lens_id":"064-982-237-295-730","lens_id":["068-749-530-080-645","064-982-237-295-730","125-933-304-897-011"],"sequence":111,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":37,"text":"Hart, K.K., et al., \"Coronary Endothelial Cell VCAM-1 Expression is Enhanced in the Diabetic Mouse Heart,\" FASEB J., 11(3):A340 (1997).","npl_type":"a","external_id":[],"lens_id":[],"sequence":112,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":38,"text":"Ikeda, Y., et al., \"Relationship between lupus nephritis activity and the serum level of soluble VCAM-1,\" Lupus, 7:347-354 (1998).","npl_type":"a","external_id":["9696139","10.1191/096120398678920172"],"record_lens_id":"060-171-436-794-036","lens_id":["153-420-025-660-689","060-171-436-794-036","101-073-287-314-17X"],"sequence":113,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":39,"text":"Issekeutz, T.B., et al., \"T Lymphocyte Migration to Arthritic Joints and Dermal Inflammation in the Rat: Differing Migration Patterns and the Involvement of VLA-4,\" Clinical Immunol. Immunopathol., 61:436-447 (1991).","npl_type":"a","external_id":["1934631","10.1016/s0090-1229(05)80014-5"],"record_lens_id":"087-826-630-512-48X","lens_id":["177-777-243-284-039","087-826-630-512-48X","114-472-014-054-94X"],"sequence":114,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":40,"text":"Jones, S.C., et al., \"Adhesion molecules in inflammatory bowel disease,\" Gut, 36:724-730 (1995).","npl_type":"a","external_id":["pmc1382677","10.1136/gut.36.5.724","7541009"],"record_lens_id":"129-840-382-982-943","lens_id":["157-496-788-658-911","129-840-382-982-943","187-850-999-373-745"],"sequence":115,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":41,"text":"Jones, S.M., et al., \"VCAM-1 expression on endothelium in lesions from cutaneous lupus erythematosus is increased compared with systemic and localized scleroderma,\" British J. Dermatol., 135:678-686 (1996).","npl_type":"a","external_id":["8977665","10.1046/j.1365-2133.1996.d01-1063.x","10.1111/j.1365-2133.1996.tb03874.x"],"record_lens_id":"033-612-650-261-814","lens_id":["121-222-222-376-224","033-612-650-261-814","127-468-472-185-592","057-683-128-490-779","002-295-963-959-518"],"sequence":116,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":42,"text":"Kallmann, B.A., et al., \"Cytokine-induced modulation of cellular adhesion to human cerebral endothelial cells is mediated by soluble vascular cell adhesion molecule-1,\" Brain, 123:687-697 (2000).","npl_type":"a","external_id":["10734000","10.1093/brain/123.4.687"],"record_lens_id":"053-683-335-676-781","lens_id":["063-518-001-313-693","053-683-335-676-781","190-378-953-906-368"],"sequence":117,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":43,"text":"Kaplanski, G., et al., \"Increased soluble vascular cell adhesion molecule 1 concentrations in patients with primary or systemic lupus erythematosus-related antiphospholipid syndrome,\" Arthritis & Rheumatism, 43(1):55-64 (2000).","npl_type":"a","external_id":["10.1002/1529-0131(200001)43:1<55::aid-anr8>3.0.co;2-m","10643700"],"record_lens_id":"093-834-990-537-522","lens_id":["107-639-365-973-516","093-834-990-537-522","159-577-294-606-65X"],"sequence":118,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":44,"text":"Kitani, A., et al., \"Soluble VCAM-1 induces Chemotaxis of Jurkat and Synovial Fluid T Cells Bearing High Affinity Very Late Antigen-4,\" U. Immun., 161:4931-4938 (1996).","npl_type":"a","external_id":["9794428"],"record_lens_id":"046-282-709-051-33X","lens_id":["063-029-116-872-666","046-282-709-051-33X"],"sequence":119,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":45,"text":"Koga, M., et al., \"Relationship Between Circulating Vascular Cell Adhesion Molecule-1 and Microvascular Complications in Type 2 Diabetes Mellitus,\" Diabet. Med., 15(8):661-667 (1998).","npl_type":"a","external_id":["10.1002/(sici)1096-9136(199808)15:8<661::aid-dia645>3.0.co;2-g","9702469"],"record_lens_id":"084-135-090-128-476","lens_id":["150-789-111-499-095","084-135-090-128-476","136-008-855-404-624"],"sequence":120,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":46,"text":"Koizumi, A., et al., \"Elevation of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in bronchial asthma,\" Clin. Exo. Immunol., 101:468-473 (1995).","npl_type":"a","external_id":["7545095","pmc1553227","10.1111/j.1365-2249.1995.tb03136.x"],"record_lens_id":"005-570-862-952-539","lens_id":["148-493-322-648-367","005-570-862-952-539","081-916-130-615-571"],"sequence":121,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":47,"text":"Kolopp-Sarda, M.N., et al., \"Longitudinal Study of Rheumatoid Arthritis Patients Discloses Sustained Elevated Serum Levels of Soluble CD016 (V-CAM),\" Clin. and Exp. Rheumatol., 19:165-170 (2001).","npl_type":"a","external_id":["11326478"],"record_lens_id":"048-272-055-967-229","lens_id":["077-622-013-815-728","048-272-055-967-229"],"sequence":122,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":48,"text":"Koskinen, P.K., et al., \"Adhesion Molecule P-Selectin and Vascular Cell Adhesion Molecule-1 in Enhanced heard Allograft Arteriosclerosis in the Rat,\" Circulation, 95(1):191-196 (1997).","npl_type":"a","external_id":["8994436","10.1161/01.cir.95.1.191"],"record_lens_id":"024-047-522-836-593","lens_id":["092-706-139-014-565","024-047-522-836-593","030-913-434-826-50X"],"sequence":123,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":49,"text":"Lai, K.N., et al., \"Upregulation of Adhesion Molecule Expression on Endothelial Cells by Anti-DNA Autoantibodies in Systemic Lupus Erythematosus,\" Clin Immunol Immunopathol, 81(3):229-238 (1996).","npl_type":"a","external_id":["10.1006/clin.1996.0183","8938099"],"record_lens_id":"010-493-825-039-067","lens_id":["098-449-199-276-368","010-493-825-039-067","093-514-665-797-715"],"sequence":124,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":50,"text":"Lee, Y.-N., et al., \"2',5'-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and affects MAP kinase activation,\" Toxicology, 179:51-60 (2002).","npl_type":"a","external_id":["10.1016/s0300-483x(02)00289-5","12204542"],"record_lens_id":"037-702-007-333-502","lens_id":["148-230-441-270-542","037-702-007-333-502","125-816-794-215-34X"],"sequence":125,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":51,"text":"Lee, S.J., et al., \"Adhesion molecule expression and regulation on cells of the central nervous system,\" J. Neuroimmunol., 98:77-88 (1998).","npl_type":"a","external_id":["10.1016/s0165-5728(99)00084-3","10430040"],"record_lens_id":"034-808-379-522-052","lens_id":["068-498-784-606-463","034-808-379-522-052","064-902-550-104-563"],"sequence":126,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":52,"text":"Li, P., et al., \"NF-KB Regulations VCAM-1 Expression on Fibroblast-Like Synoviocytes,\" J. Immunol., 164:5990-5997 (2000).","npl_type":"a","external_id":["10820282","10.4049/jimmunol.164.11.5990"],"record_lens_id":"080-901-322-038-846","lens_id":["130-597-844-936-537","080-901-322-038-846","105-195-806-544-032"],"sequence":127,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":53,"text":"Lin, C.N., et al., \"Novel Antiplatelet Constituents from Formosan Moraceous Plants,\" J. Nat. Prod., 59(9):834-838 (1996).","npl_type":"a","external_id":["10.1021/np960376j","8864236"],"record_lens_id":"004-385-281-046-625","lens_id":["127-776-620-760-46X","004-385-281-046-625","046-042-775-880-897"],"sequence":128,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":54,"text":"Ling, W.H., and Jones, P.J.H., in \"Dietary Phytosterols: A Review of Metabolism, Benefits and Side Effects,\" Life Sciences, 57(3):195-206 (1995).","npl_type":"a","external_id":["7596226","10.1016/0024-3205(95)00263-6"],"record_lens_id":"003-373-224-029-584","lens_id":["177-421-138-551-951","003-373-224-029-584","004-596-863-517-204"],"sequence":129,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":55,"text":"Liu, M., et al., \"Antimalarial Alkoxylated and Hydroxylated Chalcones: Structure-Activity Relationship Analysis,\" J. Med. Chem., 44(25):4443-4452 (2001).","npl_type":"a","external_id":["11728189","10.1021/jm0101747"],"record_lens_id":"002-911-160-091-424","lens_id":["193-985-918-365-352","002-911-160-091-424","014-288-956-078-691"],"sequence":130,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":56,"text":"Loftus, E.V., et al., \"Colonic Expression of Cell Adhesion Molecules Correlates with Clinical and Histologic Severity in Ulcerative Colitis but not Crohn's Disease,\" Gastroenterology, 108(4):A684 (1995).","npl_type":"a","external_id":["10.1016/0016-5085(95)27763-3"],"record_lens_id":"180-514-911-351-529","lens_id":["180-514-911-351-529","090-317-646-537-828"],"sequence":131,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":57,"text":"Lorini, R., et al., \"Elevated Circulating Adhesion Molecules in Children and Adolscents Affected by Insulin-Dependent Diabetes Mellitus,\" Hormone Research, 48(suppl. 2):153 (1997).","npl_type":"a","external_id":[],"lens_id":[],"sequence":132,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":58,"text":"Marinova-Mutafcheiva, L., et al., \"A Comparative Study into the Mechanisms of Action of Anti-Tumor Necrosis Factor alpha, Anti-CD4, and combined Anti-tumor Necrosis Factor alpha/Anti-CD4 Treatment in Early Collagen-Induces Arthritis,\" Arthritis Rheum., 43(3):638-644 (2000).","npl_type":"a","external_id":["10.1002/1529-0131(200003)43:3<638::aid-anr21>3.0.co;2-r","10728758"],"record_lens_id":"103-478-803-188-375","lens_id":["190-175-045-538-096","103-478-803-188-375","138-211-670-987-399"],"sequence":133,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":59,"text":"Matsuyama, T., et al., \"The Role of VCAM-1 Molecule in the Pathogenesis of Rheumatoid Synovitis,\" Hum. Cell, 9:187-191 (1996).","npl_type":"a","external_id":["9183648"],"record_lens_id":"131-948-430-283-992","lens_id":["150-019-311-841-130","131-948-430-283-992"],"sequence":134,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":60,"text":"McHale, J.F., et al., \"TNF-alpha and IL-1 Sequentially Induce Endothelial ICAM-1 and VCAM-1 Expression in MRL/lpr Lupus-Prone Mice,\" J. Immunol., 163:3993-4000 (1996).","npl_type":"a","external_id":["10491002"],"record_lens_id":"162-749-475-358-399","lens_id":["181-070-347-055-674","162-749-475-358-399"],"sequence":135,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":61,"text":"Metzger, W.J., et al., \"Anti-VLA-4 Antibody and CS-1 Peptide Inhibitor Modifies Airway Inflammation and Bronchial Airway Hyperresponsiveness in the Allergic Rabbit,\" J. Allergy Clin. Immunol., 93(No. 1, Part 2):183, Abstract No. 125 (1994).","npl_type":"a","external_id":[],"lens_id":[],"sequence":136,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":62,"text":"Miranda, C.L., et al., \"Prenylated chalcones and flavanones as inducers of quinone reductase in mouse Hepa 1c1c7 cells,\" Cancer Letters, 149:21-29 (2000).","npl_type":"a","external_id":["10.1016/s0304-3835(99)00328-6","10737704"],"record_lens_id":"013-618-395-404-882","lens_id":["014-326-336-754-745","013-618-395-404-882","075-312-058-645-893"],"sequence":137,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":63,"text":"Morales-Ducret, et al., \"Vascular Cell Adhesion Molecule-1 Expression in Synovium and on Fibroblast-Like Synoviocytes,\" J. Immunol., 149:1424-1431 (1992).","npl_type":"a","external_id":["1380043"],"record_lens_id":"073-106-406-034-539","lens_id":["109-876-776-309-312","073-106-406-034-539"],"sequence":138,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":64,"text":"Mrowka, C., et al., \"Detection of circulating adhesion molecules ICAM-1, VCAM-1 and E-Selectin in Wegener's granulomatosis, systemic lupus erythematosus and chronic renal failure,\" Clin. Nephrol., 53(5):288-299 (1995).","npl_type":"a","external_id":["7543387"],"record_lens_id":"023-462-129-297-37X","lens_id":["138-607-423-670-395","023-462-129-297-37X"],"sequence":139,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":65,"text":"Nakamura, C., et al., \"Synthesis and Biological Activities of Fluorinated Chalcone Derivatives,\" Bioorganic & Medicinal Chemistry, 10:699-706 (2002).","npl_type":"a","external_id":["10.1016/s0968-0896(01)00319-4","11814858"],"record_lens_id":"021-076-446-388-410","lens_id":["111-469-780-896-955","021-076-446-388-410","125-252-922-470-302"],"sequence":140,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":66,"text":"Nielsen, S.F., et al., \"Antileishmanial Chalcones: Statistical Design, Synthesis, and Three-Dimen-sional Quantitative Structure-Activity Relationship Analysis,\" J. Med. Chem., 41:4819-4832 (1998).","npl_type":"a","external_id":["10.1021/jm980410m","9822551"],"record_lens_id":"026-365-975-860-04X","lens_id":["075-343-822-287-297","026-365-975-860-04X","065-006-802-761-916"],"sequence":141,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":67,"text":"Nielsen, S.F., et al., \"Modifications of the alpha, beta-Double Bond in Chalcones only Marginally Affect the Antiprotozoal Activities,\" Bioorganic & Medicinal Chemistry, 6:937-945 (1998).","npl_type":"a","external_id":["10.1016/s0968-0896(98)00051-0","9730229"],"record_lens_id":"010-828-906-254-270","lens_id":["181-587-682-704-709","010-828-906-254-270","163-749-355-540-619"],"sequence":142,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":68,"text":"Nickoloff, C., et al., \"The Cytokine Network in Psoriasis,\" Arch Dermatol., 127:871-884 (1991).","npl_type":"a","external_id":["10.1001/archderm.1991.01680050115015","2036036","10.1001/archderm.127.6.871"],"record_lens_id":"053-796-807-488-721","lens_id":["141-880-420-702-764","053-796-807-488-721","191-228-158-474-001","185-257-594-157-729","129-048-753-703-941"],"sequence":143,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":69,"text":"O'Brien, K.D., et al., \"Vascular Cell Adhesion Molecule-1 is Expressed in Human Coronary Atherosclerotic Plaques,\" J. Clin. Invest., 92:945-951 (1993).","npl_type":"a","external_id":["7688768","10.1172/jci116670","pmc294934"],"record_lens_id":"089-319-030-591-942","lens_id":["110-455-871-568-371","089-319-030-591-942","179-239-946-820-082"],"sequence":144,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":70,"text":"Oguchi, S., et al., \"Monoclonal Antibody Against Vascular Cell Adhesion Molecule-1 Inhibits Neointimal Formation after Periadventitial Carotid Artery Injury in Genetically Hypercholesterolemic Mice,\" Arterioscler. Thromb. Vasc. Biol., 20:1729-1736 (2000).","npl_type":"a","external_id":["10894810","10.1161/01.atv.20.7.1729"],"record_lens_id":"020-409-729-577-47X","lens_id":["036-498-579-925-800","020-409-729-577-47X","077-869-315-068-697"],"sequence":145,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":71,"text":"Ohkawara, Y., et al., \"In Situ Expression of the Cell Adhesion Molecules in Bronchial Tissues from Asthmatics with Air Flow Limitation: In Vivo Evidence of VCAM-1/VLA-4 Interaction in Selective Eosinophil Infiltration,\" Am. J. Respir. Cell Mol. Biol., 12:4-12 (1995).","npl_type":"a","external_id":["10.1165/ajrcmb.12.1.7529029","7529029"],"record_lens_id":"037-199-944-968-523","lens_id":["155-277-670-713-29X","037-199-944-968-523","150-897-505-902-703"],"sequence":146,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":72,"text":"Orosz, C.G., et al., \"Prevention of Acute Murine Cardiac Allograft Rejection: Anti-CD4 or Anti-Vascular Cell Adhesion Molecule One Monoclonal Antibodies Block Acute Rejection but Permit Persistent Graft-Reactive Alloimmunity and Chronic Tissue Remodeling,\" J. Heart and Lung Transplantation, 16:889-904 (1997).","npl_type":"a","external_id":["9322138"],"record_lens_id":"078-842-301-994-303","lens_id":["187-499-063-232-667","078-842-301-994-303"],"sequence":147,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":73,"text":"Orosz, C.G., et al., \"Treatment with Anti-Vascular Cell Adhesion Molecule 1 Monoclonal Antibody Induces Long-Term Murine Cardiac Allograft Acceptance,\" Transportation, 56:453-460 (1993).","npl_type":"a","external_id":["10.1097/00007890-199308000-00039","7689262"],"record_lens_id":"043-411-260-236-885","lens_id":["155-569-032-499-019","043-411-260-236-885","142-217-304-303-331"],"sequence":148,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":74,"text":"Otsuki, M., et al., \"Circulating Vascular Cell Adhesion Molecule-1 as a Useful Marker for Atherosclerosis in NIDDM Patients,\" Diabetologia, 40:A440 (1997).","npl_type":"a","external_id":[],"lens_id":[],"sequence":149,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":75,"text":"Pallis, M., et al., \"Distribution of cell adhesion molecules in skeletal muscle from patients with systemic lupus erythematosus,\" Ann. Rheum. Dis., 52:667-671 (1993).","npl_type":"a","external_id":["10.1136/ard.52.9.667","pmc1005144","7694552"],"record_lens_id":"092-547-152-428-628","lens_id":["123-457-294-504-685","092-547-152-428-628","167-922-966-857-617"],"sequence":150,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":76,"text":"Papa, N.D., et al., \"Anti-endothelial cell IgG fractions from systemic lupus erythematosus patients bind to human endothelial cells and induce a pro-adhesive and a pro-inflammatory phenotype in vitro,\" Lupus, 8:423-429 (1999).","npl_type":"a","external_id":["10483009","10.1177/096120339900800603"],"record_lens_id":"089-615-129-595-851","lens_id":["104-187-464-270-230","089-615-129-595-851","126-860-106-001-204"],"sequence":151,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":77,"text":"Pelletier, R., et al., \"Analysis of Inflammatory Endothelial Changes, including VCAM-1 Expression, in Murine Cardiac Grafts,\" Transplatation, 55(2):315-320 (1993).","npl_type":"a","external_id":["7679529","10.1097/00007890-199302000-00017"],"record_lens_id":"013-523-210-518-540","lens_id":["146-868-097-010-978","013-523-210-518-540","137-811-669-366-168"],"sequence":152,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":78,"text":"Pelletier, R., et al., \"Importance of Endothelial VCAM-1 for Inflammatory Leukocytic Infiltration in Vivo,\" J. Immunol., 149(7):2473-2481 (1992).","npl_type":"a","external_id":["1382105"],"record_lens_id":"117-436-287-412-416","lens_id":["183-506-138-617-447","117-436-287-412-416"],"sequence":153,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":79,"text":"Pelletier, R., et al., \"Monoclonal Antibody to Anti-VCAM-1 Interferes with Murine Cardiac Allograft Rejection,\" Transplatation Proceedings, 25(1):839-841 (1993).","npl_type":"a","external_id":["7679845"],"record_lens_id":"027-992-140-061-177","lens_id":["106-700-002-611-421","027-992-140-061-177"],"sequence":154,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":80,"text":"Pilewski, J.M., et al., \"Cell Adhesion Molecules in Asthma: Homing, Activation, and Airway Remodeling,\" Am. J. Respir. Cell Mol. Biol., 12:1-3 (1995).","npl_type":"a","external_id":["10.1165/ajrcmb.12.1.7811464","7811464"],"record_lens_id":"038-869-867-329-897","lens_id":["081-326-025-661-138","038-869-867-329-897","081-471-527-072-756"],"sequence":155,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":81,"text":"Postigo, A.A., et al., \"Increased Binding of Synovial T Lymphocytes from Rhematoid Arthritis to Endothelial-Leykocyte Adhesion Molecule-1(ELAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1),\" J. Clin. Invest., 89:1445-1452 (1992).","npl_type":"a","external_id":["10.1172/jci115734","pmc443014","1373738"],"record_lens_id":"026-052-474-364-69X","lens_id":["147-059-870-136-380","026-052-474-364-69X","064-360-873-414-909"],"sequence":156,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":82,"text":"Rabb, H.A., et al., \"The Role of the Leukocyte Adhesion Molecules VLA-4, LFA-1, and Mac-1 in Allergic Airway Responses in the Rat,\" Am. J. Respir. Care. Med., 149:1186-1191 (1994).","npl_type":"a","external_id":["10.1164/ajrccm.149.5.8173758","8173758"],"record_lens_id":"018-826-967-709-365","lens_id":["147-076-244-818-274","018-826-967-709-365","123-003-969-684-113"],"sequence":157,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":83,"text":"Rieckmann, P., et al., \"Correlation of soluble adhesion molecules in blood and cerebrospinal fluid with magnetic resonance imaging activity in patients with multiple sclerosis,\" Mult. Scler., 4:178-182 (1998).","npl_type":"a","external_id":["9762670","10.1177/135245859800400317","10.1191/135245898678909457"],"record_lens_id":"024-548-098-881-023","lens_id":["150-931-276-820-443","024-548-098-881-023","041-023-921-941-294","056-123-695-033-417","046-048-940-398-795"],"sequence":158,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":84,"text":"Santos, J.L., et al., \"Applicability of the case-parent design in the etiological research of Type 1 diabeties in Chile and other genetically mixed populations,\" Diabetes Res. Clin. Pract., 43:143-146 (1999).","npl_type":"a","external_id":["10.1016/s0168-8227(98)00128-4","10221667"],"record_lens_id":"117-826-298-845-827","lens_id":["138-422-568-916-340","117-826-298-845-827","151-586-780-716-305"],"sequence":159,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":85,"text":"Schopf, R.E., et al., \"Soluble intercellular adhesion molecule-1 levels in patients with psoriasis,\" Br. J. Dermatol., 128:34-37 (1993).","npl_type":"a","external_id":["10.1111/j.1365-2133.1993.tb00143.x","8094011"],"record_lens_id":"047-474-123-852-175","lens_id":["061-517-205-844-835","047-474-123-852-175","064-578-589-113-844"],"sequence":160,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":86,"text":"Scudla, V., et al., \"Vascular Intercellular Adhesion Molecule-1 (VCAM-1)-a New Indicator of Activity of Systemic Lupus Erythematosus,\" Vnitr. Lek., 43:307-311 (1997).","npl_type":"a","external_id":["9601854"],"record_lens_id":"055-345-033-420-466","lens_id":["182-067-883-375-240","055-345-033-420-466"],"sequence":161,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":87,"text":"Solez K., et al., \"Adhesion molecules and rejection of renal allgrafts,\" Kidney International, 51:1476-1480 (1997).","npl_type":"a","external_id":["10.1038/ki.1997.202","9150461"],"record_lens_id":"034-961-770-644-82X","lens_id":["063-673-985-346-913","034-961-770-644-82X","199-803-039-985-326"],"sequence":162,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":88,"text":"Soriano, A., et al., \"VCAM-1, but Not ICAM-1 or MAdCAM-1, Immunoblokade Ameliorates DSS-Induces Colitis in Mice,\" Lab. Invest., 80(10):1541-1551 (2000).","npl_type":"a","external_id":["10.1038/labinvest.3780164","11045571"],"record_lens_id":"021-405-628-176-35X","lens_id":["074-751-147-613-883","021-405-628-176-35X","152-052-035-281-225"],"sequence":163,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":89,"text":"Sundell, C.L., et al., \"Suppression of VCAM-1 and MCP-1 Attenuates Atherosclerosis in LDL Receptor-knockout and ApoE-knockout Mouse Models,\" Circulation, 100(18):1-42 (1999).","npl_type":"a","external_id":[],"lens_id":[],"sequence":164,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":90,"text":"Tanio, et al., \"Differential Expression of the Cell Adhesion Molecules ICAM-1, VCAM-1, and E-Selectin in Normal and Posttransplantation Myocardium,\" Circulation, 89:1760-1768 (1994).","npl_type":"a","external_id":["10.1161/01.cir.89.4.1760","7511993"],"record_lens_id":"010-020-427-648-641","lens_id":["096-219-546-574-815","010-020-427-648-641","050-575-553-729-872"],"sequence":165,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":91,"text":"Ten Hacken, N.H.T., et al., \"Vascular cell adhesion molecules in nocturnal asthma: a possible role for VCAM-1 in ongoing airway wall inflammation,\" Clin. Exp. Allergy, 29:1518-1525 (1998).","npl_type":"a","external_id":["10.1046/j.1365-2222.1998.00426.x","10024223"],"record_lens_id":"001-931-957-594-135","lens_id":["004-667-748-711-349","001-931-957-594-135","190-491-837-617-926"],"sequence":166,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":92,"text":"Uyemura, K., et al., \"The Cytokine Network in Lesional and Lesion-Free Psoriatic Skin in Characterized by a T-Helper Type 1 Cell-Mediated Response,\" J. Invest. Dermatol., 101:701-705 (1993).","npl_type":"a","external_id":["10.1111/1523-1747.ep12371679","7693825"],"record_lens_id":"028-755-109-339-73X","lens_id":["155-690-912-696-517","028-755-109-339-73X","113-041-559-633-14X"],"sequence":167,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":93,"text":"Van Dinther-Janssen, A.C.H.M., et al., \"The VLA-4/VCAM-1 Pathway in Involved in Lymphocyte Adhesion to Endothelium in Rheumatoid Synovium,\" J. Immunol., 147(12):4207-4210 (1991).","npl_type":"a","external_id":["1721640"],"record_lens_id":"143-146-143-642-498","lens_id":["186-724-964-273-556","143-146-143-642-498"],"sequence":168,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":94,"text":"Wagner, O., et al., \"Increased Concentrations of Soluble E-Selection and V-Cam in Gestational Diabetes,\" Diabetologia, 39:A205 (1996).","npl_type":"a","external_id":[],"lens_id":[],"sequence":169,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":95,"text":"Wagner, O.F., et al., \"Putative Role of Adhesion Molecules in Metabolic Disorders,\" Hormone and Metabolic Research, 29:627-630 (1997).","npl_type":"a","external_id":["9497900","10.1055/s-2007-979114"],"record_lens_id":"079-088-812-244-154","lens_id":["191-611-253-928-472","079-088-812-244-154","084-537-274-806-368"],"sequence":170,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":96,"text":"Wang, J.P., et al., \"Investigation of the inhibitory effect of broussochalcone A on respiratory burst in neutrophils,\" European Journal of Pharmacology, 320:201-208 (1997).","npl_type":"a","external_id":["10.1016/s0014-2999(96)00888-6","9059855"],"record_lens_id":"031-891-655-955-219","lens_id":["152-744-637-845-742","031-891-655-955-219","186-703-825-158-344"],"sequence":171,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":97,"text":"Wang, S., et al., \"IL-12 Dependent Vascular Cell Adhesion Molecule-1 Expression Contributes to Airway Eosinophilic Inflammation in a Mouse Model of Asthma-Like Reaction,\" J. Immunol., 166:2741-2749 (2001).","npl_type":"a","external_id":["11160340","10.4049/jimmunol.166.4.2741"],"record_lens_id":"087-583-166-097-53X","lens_id":["157-425-281-589-293","087-583-166-097-53X","143-452-698-477-33X"],"sequence":172,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":98,"text":"Wetterrau, J.R., et al., \"An MTP Inhibitor that Normalizes Atherogenic Lipoprotein Levels in WHHL Rabbits,\" Science, 282:751-754 (Oct. 23, 1998).","npl_type":"a","external_id":["10.1126/science.282.5389.751","9784135"],"record_lens_id":"019-147-668-238-139","lens_id":["148-775-530-785-329","019-147-668-238-139","049-960-090-407-038"],"sequence":173,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}},{"npl":{"num":99,"text":"Wilkinson, L.S., et al., \"Expression of Vascular Cell Adhesion Molecule-1 in Normal and Inflamed Synovium,\" Lab. Invest., 68(1):82-88 (1993).","npl_type":"a","external_id":["7678661"],"record_lens_id":"086-363-301-215-826","lens_id":["139-504-077-521-120","086-363-301-215-826"],"sequence":174,"category":[],"us_category":[],"cited_phase":"APP","rel_claims":[]}}],"reference_cited.source":"DOCDB","reference_cited.patent_count":78,"cites_patent":true,"reference_cited.npl_count":99,"reference_cited.npl_resolved_count":89,"cites_npl":true,"cites_resolved_npl":true,"cited_by":{"patent_count":15,"patent":[{"lens_id":"158-956-680-186-802","document_id":{"jurisdiction":"US","doc_number":"11014873","kind":"B2"}},{"lens_id":"115-034-322-122-816","document_id":{"jurisdiction":"US","doc_number":"11603349","kind":"B2"}},{"lens_id":"011-383-217-691-456","document_id":{"jurisdiction":"US","doc_number":"20060063828","kind":"A1"}},{"lens_id":"177-144-375-892-087","document_id":{"jurisdiction":"US","doc_number":"9951087","kind":"B2"}},{"lens_id":"148-462-571-598-450","document_id":{"jurisdiction":"US","doc_number":"9709572","kind":"B2"}},{"lens_id":"097-859-422-215-900","document_id":{"jurisdiction":"US","doc_number":"8765812","kind":"B2"}},{"lens_id":"046-742-226-883-793","document_id":{"jurisdiction":"US","doc_number":"20080280891","kind":"A1"}},{"lens_id":"043-987-506-126-240","document_id":{"jurisdiction":"US","doc_number":"20100130497","kind":"A1"}},{"lens_id":"103-745-190-448-800","document_id":{"jurisdiction":"US","doc_number":"20160077103","kind":"A1"}},{"lens_id":"063-213-383-202-501","document_id":{"jurisdiction":"US","doc_number":"9561201","kind":"B2"}},{"lens_id":"165-629-462-589-625","document_id":{"jurisdiction":"US","doc_number":"8624056","kind":"B2"}},{"lens_id":"160-687-788-629-600","document_id":{"jurisdiction":"US","doc_number":"20060270686","kind":"A1"}},{"lens_id":"196-465-143-679-697","document_id":{"jurisdiction":"US","doc_number":"7504401","kind":"B2"}},{"lens_id":"057-212-622-531-619","document_id":{"jurisdiction":"WO","doc_number":"2011009826","kind":"A2"}},{"lens_id":"129-006-058-699-455","document_id":{"jurisdiction":"US","doc_number":"20110021815","kind":"A1"}}]},"cited_by_patent":true,"family":{"simple":{"size":17,"id":194621649,"member":[{"lens_id":"040-635-893-396-460","document_id":{"jurisdiction":"WO","doc_number":"2003053368","kind":"A3","date":"2003-09-18"}},{"lens_id":"074-502-965-540-156","document_id":{"jurisdiction":"WO","doc_number":"2003053368","kind":"A2","date":"2003-07-03"}},{"lens_id":"151-838-280-434-756","document_id":{"jurisdiction":"RU","doc_number":"2004121898","kind":"A","date":"2006-01-20"}},{"lens_id":"182-153-316-351-42X","document_id":{"jurisdiction":"CN","doc_number":"1596240","kind":"A","date":"2005-03-16"}},{"lens_id":"116-040-919-443-652","document_id":{"jurisdiction":"HU","doc_number":"P0500165","kind":"A2","date":"2006-09-28"}},{"lens_id":"125-012-528-634-732","document_id":{"jurisdiction":"EP","doc_number":"1465854","kind":"A4","date":"2005-06-08"}},{"lens_id":"067-592-035-404-500","document_id":{"jurisdiction":"EP","doc_number":"1465854","kind":"A2","date":"2004-10-13"}},{"lens_id":"102-433-279-941-758","document_id":{"jurisdiction":"JP","doc_number":"2005516941","kind":"A","date":"2005-06-09"}},{"lens_id":"094-763-515-299-60X","document_id":{"jurisdiction":"IL","doc_number":"162533","kind":"A0","date":"2005-11-20"}},{"lens_id":"091-984-075-164-348","document_id":{"jurisdiction":"US","doc_number":"20060189549","kind":"A1","date":"2006-08-24"}},{"lens_id":"031-111-113-303-072","document_id":{"jurisdiction":"CA","doc_number":"2470931","kind":"A1","date":"2003-07-03"}},{"lens_id":"157-444-405-767-906","document_id":{"jurisdiction":"TW","doc_number":"200303302","kind":"A","date":"2003-09-01"}},{"lens_id":"001-848-088-052-344","document_id":{"jurisdiction":"MX","doc_number":"PA04005864","kind":"A","date":"2004-10-29"}},{"lens_id":"188-431-610-237-076","document_id":{"jurisdiction":"US","doc_number":"20040048858","kind":"A1","date":"2004-03-11"}},{"lens_id":"111-352-037-735-89X","document_id":{"jurisdiction":"US","doc_number":"7094801","kind":"B2","date":"2006-08-22"}},{"lens_id":"168-648-365-397-35X","document_id":{"jurisdiction":"BR","doc_number":"0215240","kind":"A","date":"2004-10-26"}},{"lens_id":"074-070-273-107-689","document_id":{"jurisdiction":"AU","doc_number":"2002360763","kind":"A1","date":"2003-07-09"}}]},"extended":{"size":19,"id":194412971,"member":[{"lens_id":"040-635-893-396-460","document_id":{"jurisdiction":"WO","doc_number":"2003053368","kind":"A3","date":"2003-09-18"}},{"lens_id":"074-502-965-540-156","document_id":{"jurisdiction":"WO","doc_number":"2003053368","kind":"A2","date":"2003-07-03"}},{"lens_id":"151-838-280-434-756","document_id":{"jurisdiction":"RU","doc_number":"2004121898","kind":"A","date":"2006-01-20"}},{"lens_id":"182-153-316-351-42X","document_id":{"jurisdiction":"CN","doc_number":"1596240","kind":"A","date":"2005-03-16"}},{"lens_id":"116-040-919-443-652","document_id":{"jurisdiction":"HU","doc_number":"P0500165","kind":"A2","date":"2006-09-28"}},{"lens_id":"125-012-528-634-732","document_id":{"jurisdiction":"EP","doc_number":"1465854","kind":"A4","date":"2005-06-08"}},{"lens_id":"067-592-035-404-500","document_id":{"jurisdiction":"EP","doc_number":"1465854","kind":"A2","date":"2004-10-13"}},{"lens_id":"102-433-279-941-758","document_id":{"jurisdiction":"JP","doc_number":"2005516941","kind":"A","date":"2005-06-09"}},{"lens_id":"094-763-515-299-60X","document_id":{"jurisdiction":"IL","doc_number":"162533","kind":"A0","date":"2005-11-20"}},{"lens_id":"069-109-516-382-875","document_id":{"jurisdiction":"UA","doc_number":"81617","kind":"C2","date":"2008-01-25"}},{"lens_id":"091-984-075-164-348","document_id":{"jurisdiction":"US","doc_number":"20060189549","kind":"A1","date":"2006-08-24"}},{"lens_id":"157-444-405-767-906","document_id":{"jurisdiction":"TW","doc_number":"200303302","kind":"A","date":"2003-09-01"}},{"lens_id":"031-111-113-303-072","document_id":{"jurisdiction":"CA","doc_number":"2470931","kind":"A1","date":"2003-07-03"}},{"lens_id":"001-848-088-052-344","document_id":{"jurisdiction":"MX","doc_number":"PA04005864","kind":"A","date":"2004-10-29"}},{"lens_id":"188-431-610-237-076","document_id":{"jurisdiction":"US","doc_number":"20040048858","kind":"A1","date":"2004-03-11"}},{"lens_id":"151-195-074-177-49X","document_id":{"jurisdiction":"ZA","doc_number":"200404808","kind":"B","date":"2005-08-30"}},{"lens_id":"111-352-037-735-89X","document_id":{"jurisdiction":"US","doc_number":"7094801","kind":"B2","date":"2006-08-22"}},{"lens_id":"168-648-365-397-35X","document_id":{"jurisdiction":"BR","doc_number":"0215240","kind":"A","date":"2004-10-26"}},{"lens_id":"074-070-273-107-689","document_id":{"jurisdiction":"AU","doc_number":"2002360763","kind":"A1","date":"2003-07-09"}}]}},"has_sequence":false,"legal_status":{"ipr_type":"patent for invention","granted":true,"earliest_filing_date":"2002-12-19","grant_date":"2006-08-22","anticipated_term_date":"2023-04-11","discontinuation_date":"2014-09-22","has_disclaimer":true,"patent_status":"EXPIRED","publication_count":2,"has_spc":false,"has_grant_event":false,"has_entry_into_national_phase":false},"abstract":{"en":[{"text":"The invention relates to compounds, pharmaceutical compositions and methods of using compounds of the general formula or its pharmaceutically acceptable salt or ester, wherein the substituents are defined in the application.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"}]},"abstract_lang":["en"],"has_abstract":true,"claim":{"en":[{"text":"1. A compound of Formula I or its pharmaceutically acceptable salt or ester, wherein: the wavy line indicates that the compound can be in the form of the E- or Z- isomer; R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 2β , R 3β , R 4β , R 5β or R 6β , or one of R 2α , R 3α , R 4α , R 5α or R 6α must be a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl; wherein when one of R 2β , R 3β , R 4β , R 5β or R 6β is a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl, only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and wherein when one of R 2β , R 3β , R 4β , R 5β or R 6β is a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl, only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one sulfur, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; or at least one of R 2α , R 3α , R 4α , R 5α , R 6α or one of R 2β , R 3β , R 4β , R 5β , R 6β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, (CH 2 ) y C(O)OH, wherein is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 , and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"2. The compound of claim 1 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 2β , R 3β , R 4β , R 5β or R 6β , or one of R 2α , R 3α , R 4α , R 5α or R 6α must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl; wherein when one of R 2β , R 3β , R 4β , R 5β or R 6β is a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and wherein when one of R 2β , R 3β , R 4β , R 5β or R 6β is a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one sulfur, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and at least one of R 2α , R 3α , R 4α , or one of R 2β , R 3β , R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"3. The compound of claim 1 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein when one of R 2β , R 3β , R 4β , R 5β or R 6β is a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one sulfur, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and with the proviso that at least one of R 2α , R 3α , R 4α , or one of R 2β , R 3β , R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"4. The compound of claim 3 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"5. The compound of claim 4 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"6. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, beteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"7. The compound of claim 6 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"8. The compound of claim 7 or its pharmaceutically acceptable salt or ester, wherein: R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"9. The compound of claim 8 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, heterocyclicamino lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, dialkylamino, N(R 2 ) 2 , —NR 7 R 8 , tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 8-membered monocyclic or benzoftlsed ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"10. The compound of claim 9 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, lower alkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, heteroaryl lower alkoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, carboxy, —C(O)OR 2 , —C(O)N(R 2 ) 2 , and —C(O)NR 7 R 8 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, hydroxy, hydroxyalkyl, heterocyclic, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N( 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, and lower alkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 5- to 7-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from carboxy or —C(O)OR 2 ; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"11. The compound of claim 10 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, and carboxy, all of which can be optionally substituted; by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"12. The compound of claim 11 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"13. The compound of claim 12 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked saturated thienyl or benzothienyl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"14. The compound of claim 13 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, fluorine, chlorine, methoxy, ethoxy, propoxy, 3-(1-morpholino) propoxy, 2-(1-morpholino) ethoxy, CH 3 O(CH 2 ) 2 O(CH 2 ) 2 —, wherein one of R 4β , R 5β or R 6β must be selected from the group consisting of thiophen-2-yl, thiophen-3-yl, benzo[b]thiophen-2-yl, benzo[b]thiophen-3-yl, with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"15. The compound of claim 14 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, methoxy, 3-(1-morpholino) propoxy, 2-(1-morpholino) ethoxy, and CH 3 O(CH 2 ) 2 O(CH 2 ) 2 ; wherein one of R 4β , R 5β or R 6β must be selected from the group consisting of thiophen-2-yl, benzo[b]thiophen-2-yl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"16. The compound of claim 15 selected from the group consisting of: 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid; 4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 2-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid; 4-[3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 2-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid, sodium salt; 4-[3E-(4-Thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3-{4-(thien-2-yl)-phenyl}-3-oxo-E-propenyl]-benzoic acid, sodium salt; 4-[3-{4-(thien-2-yl)-phenyl}-3-oxo-E-propenyl]-benzoic acid; 4-[3-(2-Methoxy-4-thiophen-2-yl-phenyl)-3-oxo-E-propenyl]-benzoic acid; 4-[3E-(4-Pyrrolidin-1-yl-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-{4-Fluoro-3-(thiophen-2-yl)-phenyl}-acryloyl]-benzoic acid; 4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid; 4-[3E-(2-Fluoro-4-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(2-Cyclopropylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(4-Methoxy-2-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 2-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 2-[3E-(2,6-Dimethoxy-4-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(2,4-Dimethoxy-6-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-{3E-[2,4-Dimethoxy-5-(5-methyl-thiophen-2-yl)-phenyl]-acryloyl}-benzoic acid; 4-[3E-(4-Methoxy-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(3-Thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 3-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(3-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid; 4-[3E-(2-Methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-{3E-[4-(1-Carboxy-1-methyl-ethoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid; 2-[3E-(4-Methoxy-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-(3E-{2-Methoxy-4-[2-(2-methoxy-ethoxy)-ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic acid; 4-{3E-[4-(3-Hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid; 5-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid methyl ester; 5-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid; 4-[3E-(4-Ethoxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(4-Hydroxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid, sodium salt; 4-[3E-(2-Hydroxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-{3E-[2-(1-Carboxy-1-methyl-ethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid; 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride; 4-{3E-[2-(3,5-Dimethyl-isoxazol-4-ylmethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid; 4-[3E-(2-Pyrrolidin-1-yl-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-{3E-[2-(3-Hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid; 4-{3E-[2-(3-Morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride; 4-{3E-[4-Methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride; 4-[3E-(2-Dimethylcarbamoylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(4-Methoxy-2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-[3E-(2-Carbamoylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-2-oxo-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid; 4-(3E-{4-Methoxy-2-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic acid, hydrochloride; 2-{4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-2-methyl-propionic acid; and 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid ethyl ester, or its pharmaceutically acceptable salt or ester.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"17. The compound of claim 16 selected from the group consisting of: 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid; 4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid; 4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid; and 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride,or its pharmaceutically acceptable salt or ester.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"18. The compound of claim 17 wherein the compound is 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid or its pharmaceutically acceptable salt or ester.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"19. The compound of claim 17 wherein the compound is 4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid, or its pharmaceutically acceptable salt or ester.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"20. The compound of claim 17 wherein the compound is 4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid; and,or its pharmaceutically acceptable salt or ester.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"21. The compound of claim 17 wherein the compound is 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride,or its pharmaceutically acceptable salt or ester.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"22. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"23. The compound of claim 22 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein when one of R 4β , R 5β , R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso at least one of R 2α , R 3α , R 4α must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"24. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein when one of R 4β , R 5β , R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso at least one of R 2α , R 3α , R 4α must be selected from the group consisting of thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"25. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein when one of R 4β , R 5β , R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"26. The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein when one of R 4β , R 5β , R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"27. The compound of claim 3 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl loweralkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein when one of R 4β , R 5β , R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; and with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"28. The compound of claim 3 or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein when one of R 4β , R 5β , R 6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 , wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"29. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , or 28 , together with one or more pharmaceutically acceptable carrier.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"30. A method for the treatment of an inflammatory disorder, comprising administering an effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , or 28 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"31. The method of claim 30 , wherein the disorder is arthritis.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"32. The method of claim 30 , wherein the disorder is rheumatoid arthritis.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"33. The method of claim 30 , wherein the disorder is asthma.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"34. The method of claim 30 , wherein the treatment is disease modifying for the treatment of rheumatoid arthritis.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"35. The method of claim 30 , wherein the disorder is allergic rhinitis.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"36. The method of claim 30 , wherein the disorder is chronic obstructive pulmonary disease.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"37. The method of claim 30 , wherein the disorder is atherosclerosis.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"38. The method of claim 30 , wherein the disorder is restinosis.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"39. A method for inhibiting the expression of VCAM-1, comprising administering an effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , or 28 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"}]},"claim_lang":["en"],"has_claim":true,"description":{"en":{"text":"This patent application claims priority to U.S. Provisional Patent Application Ser. No. 60/342,034 filed Dec. 19, 2001 and U.S. Provisional Patent Application Ser. No. 60/386,482 filed Jun. 5, 2002. The present invention is in the field of novel chalcone derivatives, pharmaceutical compositions and methods for treating a variety of diseases and disorders, including inflammation and cardiovascular disease. BACKGROUND OF THE INVENTION Adhesion of leukocytes to the endothelium represents a fundamental, early event in a wide variety of inflammatory conditions, autoimmune disorders and bacterial and viral infections. Leukocyte recruitment to endothelium is mediated in part by the inducible expression of adhesion molecules on the surface of endothelial cells that interact with counterreceptors on immune cells. Endothelial cells determine which types of leukocytes are recruited by selectively expressing specific adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. VCAM-1 binds to the integrin VLA-4 expressed on lymphocytes, monocytes, macrophages, eosinophils, and basophils but not neutrophils. This interaction facilitates the firm adhesion of these leukocytes to the endothelium. VCAM-1 is an inducible gene that is not expressed, or expressed at very low levels, in normal tissues. VCAM-1 is upregulated in a number of inflammatory diseases, including arthritis (including rheumatoid arthritis), asthma, dermatitis, psoriasis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. Coronary heart disease (CHD), primarily as a result of atherosclerosis, remains the leading cause of death in industrialized countries. Atherosclerosis is a disease characterized by vascular inflammation, deposition of lipids in the arterial vessel wall and smooth muscle cell proliferation resulting in a narrowing of the vessel passages. In advanced stages of the disease atherosclerotic lesions can become unstable resulting in plaque rupture, thrombosis, myocardial infarction and ischemic heart disease. It is now well accepted that the initiating events in atherosclerosis are local injury to the arterial endothelium that results in the induction of VCAM-1 and recruitment of mononuclear leukocytes that express the integrin counterreceptor, VLA-4, (O'Brien, et al., J. Clin. Invest., 92: 945–951, 1993). Subsequent conversion of leukocytes to foamy macrophages results in the synthesis of a wide variety of inflammatory cytokines, growth factors, and chemoattractants that help propagate formation of the mature atheromatous plaque by further inducing endothelial activation, leukocyte recruitment, smooth muscle cell proliferation, and extracellular matrix deposition. Pharmacological inhibition of VCAM-1 expression has been shown to inhibit atherosclerosis in several animal models (Sundell et al., Circulation, 100: 42, 1999). A monoclonal antibody against VCAM-1 has also been shown to inhibit neointimal formation in a mouse model of arterial wall injury (Oguchi, S., et al., Arterioscler. Thromb. Vasc. Biol., 20: 1729–1736, 2000). Asthma, which is increasing in prevalence and morbidity world-wide, is a chronic inflammatory disease characterized by lung eosinophilia and bronchial hyperreactivity. The interaction between VCAM-1 on lung endothelial cells and VLA-4, which is the integrin counterreceptor expressed on eosinophils, is thought to be important for selective eosinophil recruitment. Eosinophils have been considered an important effector cell in the pathogenesis of asthma and other allergic diseases. Activated eosinophils release proteins such as major basic protein (MBP) that have been demonstrated to induce bronchial hyperreactivity, one of the defining criteria of asthma (Bousquot, et al., N. Engl. J. Med., 323: 1033–1039, 1990). It has been demonstrated that VCAM-1 is markedly upregulated on human bronchial vascular endothelium of subjects with asthma who have air flow limitation, when compared with subjects without asthma (Pilewski, et al., Am. J. Respir. Cell Mol. Biol., 12, 1–3, 1995; Ohkawara, Y., et al., Am. J. Respir. Cell Mol. Biol., 12, 4–12, 1995; Gosset, P., et al., Int. Arch. Allergy Immunol. 106: 69–77, 1995; Hacken, N. H., et al., Clin. Exp. Allergy, 28 (12): 1518–1525, 1998). An elevation in serum soluble VCAM-1 levels has also been demonstrated in patients undergoing a bronchial asthma attack compared with levels under stable conditions (Montefort, S., Koizumi, A., Clin. Exp. Immunol., 101: 468–73, 1995). Several animal studies further demonstrate a spatial and temporal association between VCAM-1 and asthma. In a mouse model of allergic asthma, VCAM-1 expression was shown to be induced by allergen challenge, and administration of an anti-VCAM-1 antibody was effective in inhibiting eosinophil infiltration that occurred in this model (Metzger, W. J., et al., J. Allergy Clin. Immunol., 93: 183, 1994). Further evidence for the importance of VCAM-1 in allergic asthma comes from work in IL-12 knockout mice. IL-12 knockout mice had fewer eosinophils and VCAM-1 expression than wildtype mice; however, administration of recombinant IL-12 at the time of ova sensitization and challenge restored lung VCAM-1 expression and eosinophilia (Wang, S., et al., J. Immunol., 166:2741–2749, 2001). There are several examples where blocking the integrin receptors for VCAM-1 have had positive effects on animal models of asthma (Rabb et al., Am. J. Respir. Care Med. 149: 1186–1191, 1994; Abraham, W, et al., Am. J. Respir. Crit. Care Med. 156: 696–703. 1997) further demonstrating the importance of VCAM-1/VLA-4 interactions in allergic inflammation. Eosinophils are also important effector cells in allergic rhinitis. VCAM-1 has been demonstrated to be upregulated 24 hrs after nasal allergen provocation in patients with seasonal allergic rhinitis but not in normal subjects (Braunstahl, G. J., et al., J. Allergy Clin. Immunol., 107: 469–476, 2001). Rheumatoid arthritis (RA) is a clinical syndrome of unknown cause characterized by symmetric, polyarticular inflammation of synovial-lined joints. The role of adhesion molecules in the pathogenesis of RA has also been well documented, and VCAM-1 expression on synovial fibroblasts is a clinical hallmark of RA (Li, P., et al., J. Immunol. 164: 5990–7, 2000). VLA-4/VCAM-1 interactions may be the predominant mechanism for recruitment of leukocytes to the synovium (Dinther-Janssen, et al., J. Immunol. 147: 4207–4210, 1991; Issekeutz and Issekeutz, Clin. Immunol. Immunopathol. 61:436–447, 1991; Morales-Ducret et al., J. Immunol. 149:1424–1431, 1992; Postigo et al., J. Clin. Invest. 89:1445–1452, 1992; Matsuyama, T., et al, Hum. Cell, 9: 187–192, 1996). In support of this, increased VCAM-1 expression has been found in RA synovial tissue compared with osteoarthritis and control tissue (Wilkinson et al., Lab. Invest. 69:82–88, 1993; Furuzawa-Carballeda, J., et al., Scand. J. Immunol. 50: 215–222; 1999). Soluble VCAM-1 is higher in RA patients than in control subjects (Kolopp-Sarda, M. N., et al., Clin. Exp. Rheumatol. 19: 165–70, 2001). Soluble VCAM-1 has been shown to be chemotactic for T cells (Kitani, A., et al., J. Immun. 161: 4931–8, 1998), and in addition to being a possible diagnostic marker for RA, may contribute to its pathogenesis by inducing migration and recruitment of T cells. VCAM-1 expressed on fibroblast-like synoviocytes has also been implicated in enhanced survival of activated synovial fluid B cells (Marinova, Mutafcheia, L., Arthritis Rheum. 43: 638–644, 2000) that may further contribute to RA pathogenesis. Chronic inflammation and accompanying vascular complications and organ damage characterize systemic lupus erythematosis (SLE). Recent studies suggest that VCAM-1 plays a role in SLE. Expression of VCAM-1 is increased on dermal vessel endothelial cells in patients with active systematic lupus erythematosus (Jones, S. M., British J. Dermatol. 135: 678–686, 1996) and correlates with increased disease severity (Belmont et al., Arthritis Rheum. 37:376–383, 1994). SLE muscle samples with perivascular infiltrate have greater endothelial cell expression of VCAM-1 compared with SLE patients without a perivascular infiltrate or with control samples (Pallis et al., Ann. Rheum. Dis. 52:667–671, 1993). Increased expression of VCAM-1 has also been demonstrated in kidneys of lupus-prone MRL/lpr mice compared to nonautoimmune strains and its expression increased with disease severity (McHale, J. F., et al., J. Immunol. 163: 3993–4000, 1999). VCAM-1 expression on mesangial cells in vitro can be stimulated by IL-1, TNF-α, and INFγ exposure as well as by anti-endothelial cell IgG fraction and anti-DNA autoantibodies from SLE patients (Wuthrich, Kidney Int. 42: 903–914, 1992; Papa, N. D., et al., Lupus, 8: 423–429, 1999; Lai, K. N., et al., Clin Immunol Immunopathol, 81: 229–238, 1996). Furthermore, soluble VCAM-1 is higher in SLE patients than in normal subjects (Mrowka, C., et al., Clin. Nephrol. 43: 288–296, 1995; Baraczka, K., et al., Acta. Neuro. Scand. 99: 95–99, 1999; Kaplanski, G., et al., Arthritis Rheumol. 43: 55–64, 2000; Ikeda, Y., Lupus, 7: 347–354, 1998) and correlates with disease activity (Scudla, V., Vnitr. Lek., 43: 307–311, 1997). Increased VCAM-1 expression has also been demonstrated in solid organ transplant rejection. Acute transplant rejection occurs when the transplant recipient recognizes the grafted organ as “non-self” and mounts an immune response characterized by massive infiltration of immune cells, edema, and hemorrage that result in the death of the transplanted organ. Acute rejection occurs in a matter of hours or days and has been correlated with increased levels of VCAM-1 in tissues and in plasma (Tanio et al., Circulation, 89:1760–1768, 1994; Cosimi et al., J. Immunol. 144: 4604–4612, 1990; Pelletier, R., et al., Transplantation, 55: 315, 1992). A monoclonal antibody to VCAM-1 has been shown to inhibit cardiac allograft rejection in mice (Pelletier, R., J. Immunol., 149: 2473–2481, 1992; Pelletier, R., et al., Transplantation Proceedings, 25: 839–841, 1993; Orosz, C. G., et al., J. Heart and Lung Transplantation, 16: 889–904, 1997) and when given for 20 days can cause complete inhibition of rejection and long-term graft acceptance (Orosz C. G., et al., Transplantation, 56: 453–460, 1993). Chronic graft rejection also known as allograft vasculopathy is distinct from acute transplant rejection and is a leading cause of late graft loss after renal and heart transplantation. Histologically it is characterized by concentric neointimal growth within vessels that is largely due to smooth muscle migration and proliferation. It is thought to be the result of endothelial damage brought about by several factors including: ischemia-reperfusion injury, immune complexes, hypertension, hyperlipidemia and viruses. All of these factors have been associated with induction of VCAM-1 in endothelial cells. There is also a strong correlation of soluble and tissue VCAM-1 levels with chronic rejection (Boratynska, M.,. Pol. Arch. Med. Wewn, 100: 410–410, 1998; Zembala, M., et al., Ann. Transplant. 2: 16–9, 1998; Solez K., et al., Kidney International., 51: 1476–1480, 1997; Koskinen P. K., et al., Circulation, 95: 191–6, 1997). Multiple sclerosis is a common demyelinating disorder of the central nervous system, causing patches of sclerosis (plaques) in the brain and spinal cord. It occurs in young adults and has protean clinical manifestations. It is well documented that VCAM-1 is expressed on brain microvascular endothelial cells in active lesions of multiple sclerosis (Lee S. J., et al., J. Neuroimmunol., 98: 77–88, 1998). Experimental therapy of experimental autoimmune encephalomyelitis, which is an animal model for multiple sclerosis, using antibodies against several adhesion molecules, including VCAM-1, clearly shows that adhesion molecules are critical for the pathogenesis of the disease (Benveniste et al., J. Neuroimmunol. 98:77–88, 1999). A time and dose dependent expression of VCAM-1 and release of soluble VCAM-1 were detected in cultures of human cerebral endothelial cells induced by TNFα, but not in peripheral blood mononuclear cells (Kallmann et al., Brain, 123:687–697, 2000). Clinical data also show that adhesion molecules in blood and cerebrospinal fluid are up-regulated throughout the clinical spectrum of multiple sclerosis (Baraczka, K., et al., Acta. Neurol. Scand. 99: 95–99, 1999; Reickmann, P., et al., Mult. Scler., 4: 178–182, 1998; Frigerio, S., et al., J. Neuroimmunol., 87: 88–93, 1998) supporting the notion that therapies which interfere with cell adhesion molecules such as VCAM-1 may be beneficial in modifying this disease (Elovaara et al., Arch. Neurol. 57:546–551, 2000). Diabetes mellitus is a metabolic disease in which carbohydrate utilization is reduced and that of lipid and protein is enhanced. Evidence has accumulated that increased levels of adhesion molecules may play a functional pathophysiological role in diabetes (Wagner and Jilma, Hormone and Metabolic Research, 29: 627–630, 1997; Kado, S., Diabetes Res. Clin. Pract., 46: 143–8, 1999). It is caused by an absolute or relative deficiency of insulin and is characterized by chronic hyperglycemia, glycosuria, water and electrolyte loss, ketoacidosis, and coma. Elevated circulating adhesion molecules including VCAM-1 have been detected in patients with diabetes and in experimental models of diabetes in animals (Lorini et al., Hormone Research, 48: 153, 1997; Otsuki et al., Diabetologia, 40: A440, 1997; Hart et al., FASEB J. 11:A340, 1997; Albertini et al., Diabetologia, 39: A240, 1996; Wagner et al., Diabetologia, 39: A205, 1996; Enghofer et al., Diabetologia, 39: A97, 1996; Koga M., Diabet. Med., 15: 661–667, 1998). In addition, complications of diabetes often include peripheral vasculopathies such as diabetic retinopathy and diabetic nephropathy. It is believed that adhesion of leukocytes to the peripheral vasculature plays a central role in the vasculopathies often associated with diabetes. Crohn's disease, also known as regional enteritis, is a subacute chronic inflammatory condition of unknown cause, involving the internal ileum and less frequently other parts of the gastrointestinal tract. It is characterized by patchy deep ulcers that may cause fistulas, and narrowing and thickening of the bowel by fibrosis and lymphocytic infiltration. Ulcerative colitis is a chronic disease of unknown cause characterized by ulceration of the colon and rectum, with rectal bleeding, mucosal crypt abscesses, inflammatory pseudopolyps, abdominal pain, and diarrhea. It has been reported that serum VCAM-1 reflects the grade of intestinal inflammation in patients with Crohn's disease or ulcerative colitis (Jones, et al., Gut, 36: 724–30, 1995; Goggins et al., Gastroenterology, 108: A825, 1995; Goeke and Manns, Gastroenterology, 106: A689, 1994; Goeke et al., J. Gasterokenterol. 32:480–486, 1997; Loftus et al., Gastroenterology, 108: A684, 1995; Tahami et al., Gastroenterology, 118: A344, 2000). Antibodies to VCAM-1 have been shown to ameliorate experimentally-induced colitis in mice (Soriano, A., Lab. Invest. 80: 1541–1551, 2000). Psoriasis is a chronic skin disease characterized by erythematous scaling plaques as a result of keratinocyte hyperplasia, influx of immune cells and endothelial activation (Nickoloff, B. J., et al., J. Invest. Dermatol., 127: 871–884, 1991). VCAM-1 is upregulated in psoriatic skin as compared to normal skin (Groves, R. W., J. Am. Acad. Dermatol., 29: 67–72, 1993; Uyemura, K., et al., J. Invest. Dermatol. 101: 701–705, 1993) and levels of circulating VCAM-1 correlate with disease activity (Schopf, R. E., Br. J. Dermatol., 128: 34–7, 1993). U.S. Pat. Nos. 5,750,351; 5,807,884; 5,811,449; 5,846,959; 5,773,231, and 5,773,209 to Medford, et al., as well as the corresponding WO 95/30415 to Emory University indicate that polyunsaturated fatty acids (“PUFAs”) and their hydroperoxides (“ox-PUFAs”), which are important components of oxidatively modified low density lipoprotein (LDL), induce the expression of VCAM-1, but not intracellular adhesion molecule-1 (ICAM-1) or E-selectin in human aortic endothelial cells, through a mechanism that is not mediated by cytokines or other noncytokine signals. This is a fundamental discovery of an important and previously unknown biological pathway in VCAM-1 mediated immune responses. As non-limiting examples, linoleic acid, linolenic acid, arachidonic acid, linoleyl hydroperoxide (13-HPODE) and arachidonic hydroperoxide (15-HPETE) induce cell-surface gene expression of VCAM-1 but not ICAM-1 or E-selectin. Saturated fatty acids (such as stearic acid) and monounsaturated fatty acids (such as oleic acid) do not induce the expression of VCAM-1, ICAM-1 or E-selectin. WO 98/51662, filed by AtheroGenics, Inc. and listing as inventors Russell M. Medford, Patricia K. Somers, Lee K. Hoong, and Charles Q. Meng, claims priority to provisional application U.S. Ser. No. 60/047,020, filed on May 14, 1997. This application discloses the use of a broad group of compounds as cardiovascular protectants that exhibit at least one, and sometimes a composite profile, of reducing cholesterol, lowering LDL, and inhibiting the expression of VCAM-1. U.S. Pat. No. 5,155,250 to Parker, et al. discloses that 2,6-dialkyl-4-silylphenols are antiatherosclerotic agents. The same compounds are disclosed as serum cholesterol lowering agents in PCT Publication No. WO 95/15760, published on Jun. 15, 1995. U.S. Pat. No. 5,608,095 to Parker, et al. discloses that alkylated-4-silyl-phenols inhibit the peroxidation of LDL, lower plasma cholesterol, and inhibit the expression of VCAM-1, and thus are useful in the treatment of atherosclerosis. WO 98/51289, which claims priority to provisional application U.S. Ser. No. 60/047,020, filed on May 14, 1997 by Emory University listing Patty Somers as sole inventor, discloses the use of a group of compounds as cardiovascular protectants and antiinflammatory agents which exhibit at least one, and sometimes a composite profile, of reducing cholesterol, lowering LDL, and inhibiting the expression of VCAM-1 and thus can be used as antiinflammatory and cardivascular treating agents. U.S. Pat. Nos. 5,380,747; 5,792,787; 5,783,596; 5,750,351; 5,821,260; 5,807,884; 5,811,449; 5,846,959; 5,877,203; and 5,773,209 to Medford, et al., teach the use of dithiocarbamates of the general formula A-SC(S)-B for the treatment of cardiovascular and other inflammatory diseases. Examples include sodium pyrrolidine-N-carbodithioate, trisodium N,N-di(carboxymethyl)-N-carbodithioate, and sodium N,N-diethyl-N-carbodithioate. The patents teach that the compounds inhibit the expression of VCAM-1. WO 98/23581 discloses the use of benzamidoaldehydes and their use as cysteine protease inhibitors. WO 97/12613 of Cornicelli et al. discloses compounds for the inhibition of 15-lipogenase to treat and prevent inflammation or atherosclerosis. Compounds disclosed include benzopyranoindole, benzimidazole, catacholes, benzoxadiazines, benzo[a]phenothiazine, or related compounds thereof. Japanese Patent No. 06092950 to Masahiko et al. discloses preparation of epoxy compounds wherein electron deficient olefins such as acylstyrene derivatives, styrene derivatives, and cyclohexenone derivatives are efficiently oxidized by a hydrogen peroxide derivative in the presence of a primary or secondary amine in an organic solvent to give said epoxides which are useful intermediates for pharmaceutical and flavoring materials. U.S. Pat. No. 5,217,999 to Levitzki et al. discloses substituted styrene compound as a method of inhibiting cell proliferation. Chalcone (1,3-bis-aromatic-prop-2-en-1-ones) compounds are natural products related to flavonoids. WO 99/00114 (PCT/DK98/00283) discloses the use of certain chalcones, 1,3-bis-aromatic-propan-1-ones (dihydrochalcones), and 1,3-bisaromatic-prop-2-yn-1-ones for the preparation of pharmaceutical compositions for the treatment of prophylaxis of a number of serious diseases including i) conditions relating to harmful effects of inflammatory cytokines, ii) conditions involving infection by Helicobacter species, iii) conditions involving infections by viruses, iv) neoplastic disorders, and v) conditions caused by microorganisms or parasites. WO 00/47554 filed by Cor Therapeutics describes a broad class of substituted unsaturated compounds for use as antithrombotic agents. WO 96/20936 (PCT/KR95/00183) discloses thiazolidin-4-one derivatives of the formula: which act as PAF antagonists or 5-lipoxygenase inhibitors. The compounds are used in the prevention and treatment of inflammatory and allergic disorders mediated by platelet-activating factor and/or leukotrienes. U.S. Pat. No. 4,085,135 discloses 2′-(carboxymethoxy)-chalcones with antigastric and antiduodenal ulcer activities. U.S. Pat. No. 5,744,614 to Merkle et al. discloses a process for preparing 3,5-diarylpyrazoles and various derivatives thereof by reacting hydrazine hydrate with 1,3-diarylpropenone in the presence of sulfuric acid and an iodine compound. U.S. Pat. No. 5,951,541 to Wehlage et al. discloses the use of salts of aromatic hydroxy compounds, such as (hydroxyaryl)alkenone salts, as brighteners in aqueous acidic electroplating baths. In addition the invention discloses that such compounds have a lower vapor pressure than the known brighteners, as a single substance and in the electroplating baths, in order to avoid losses of substance. They also have high water solubility properties. Japanese Patent No. 07330814 to Shigeki et al. discloses benzylacetophenone compounds as photoinitiator compounds. Japanese Patent No. 04217621 to Tomomi discloses siloxane chalcone derivatives in sunscreens. U.S. Pat. No. 4,085,135 to Kyogoku et al. discloses a process for preparation of 2′-(carboxymethoxy)-chalcones having antigastric and anti duodenal activities with low toxicity and high absorptive ratio in the body. This patent suggests that the high absorptive ratio in the body is due to the 2′-carboxymethoxy group attached to the chalcone derivative. U.S. Pat. No. 4,855,438 discloses the process for preparation of optically active 2-hydroxyethylazole derivatives which have fungicidal and plant growth-regulating action by reacting an α-β-unsaturated ketone which could include a chalcone or a chalcone derivative with an enantiomerically pure oxathiolane in the presence of a strongly basic organometallic compound and at temperatures ranging from −80 to 120° C. European Patent No 307762 assigned to Hofmann-La Roche discloses substituted phenyl chalcones. E. Bakhite et al. in J. Chem. Tech. Biotech. 1992, 55, 157–161, have disclosed a process for the preparation of some phenyloxazole derivatives of chalcone by condensing 5-(p-acetylphenyl)-2-phenyloxazole with aromatic aldehydes. Herencia, et al., in Synthesis and Anti-inflammatory Activity of Chalcone Derivatives, Bioorganic & Medicinal Chemistry Letters 8 (1998) 1169–1174, discloses certain chalcone derivatives with anti-inflammatory activity. Hsieh, et al., Synthesis and Antiinflammatory Effect of Chalcones, J. Pharm. Pharmacol. 2000, 52; 163–171 describes that certain chalcones have potent antiinflammatory activity. Zwaagstra, et al., Synthesis and Structure-Activity Relationships of Carboxylated Chalcones: A Novel Series of CysLT 1 (LT 4 ) Receptor Antagonists; J. Med. Chem., 1997, 40, 1075–1089 discloses that in a series of 2-, 3-, and 4-(2-quinolinylmethoxy)- and 3- and 4-[2-(2-quinolinyl)ethenyl]-substituted, 2′, 3′, 4′, or 5′ carboxylated chalcones, certain compounds are CysLT 1 receptor antagonists. JP 63010720 to Nippon Kayaku Co., LTD discloses that chalcone derivatives of the following formula (wherein R 1 and R 2 are hydrogen or alkyl, and m and n are 0–3) are 5-lipoxygenase inhibitors and can be used in treating allergies. JP 06116206 to Morinaga Milk Industry Co. Ltd, Japan, discloses chalcones of the following structure as 5-lipoxygenase inhibitors, wherein R is acyl and R 1 –R 5 are hydrogen, lower alkyl, lower alkoxy or halo, and specifically that in which R is acyl and R 1 –R 5 are hydrogen. U.S. Pat. No. 6,046,212 to Kowa Co. Ltd. discloses heterocyclic ring-containing chalcones of the following formula as antiallergic agents, wherein A represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, or a group: in which X represents a hydrogen or halogen atom or a hydroxyl, lower alkyl or lower alkoxyl group and B represents —CH═CH—,—N(R 6 )—, R 6 is a lower alkyl group or a lower alkoxyalkyl group, —O— or —S—; W represents —CH═CH— or —CH 2 O—, and R 1-5 is the same or different and each independently represent a hydrogen or halogen atom, a hydroxyl, a lower alkyl, lower alkoxyl, carboxyl, cyano, alkyloxycarbonyl or tetrazolyl group, a group —CONHR 7 in which R 7 represents a hydrogen atom or a lower alkyl group, or a group —O(CH 2 ) n R 8 in which R 8 represents a carboxyl, alkyloxycarbonyl or tetrazolyl group and n is from 1 to 4, with the proviso that at least one of the groups R 1-5 represents a carboxyl, cyano, alkyloxycarbonyl or tetrazolyl group, the group —CONHR 7 or the group —O(CH 2 )nR 8 ; or a salt or solvate thereof. Reported bioactivies of chalcones have been reviewed by Dimmock, et al., in Bioactivities of Chalcones, Current Medicinal Chemistry 1999, 6, 1125–1149; Liu et al., Antimalarial Alkoxylated and Hydroxylated Chalones: Structure-Activity Relationship Analysis, J. Med. Chem. 2001, 44, 4443–4452; Herencia et al, Novel Anit-inflammatory Chalcone Derivatives Inhibit the Induction of Nitric Oxide Synthase and Cyclooxygenase-2 in Mouse Peritoneal Macrophages, FEBS Letters, 1999, 453, 129–134; and Hsieh et al., Synthesis and Anti-inflammatory Effect of Chalcones and Related Compounds, Pharmaceutical Research, 1998, Vol.15, No. 1, 39–46. Given that VCAM-1 is a mediator of chronic inflammatory disorders, it is a goal of the present work to identify new compounds, compositions and methods that can inhibit the expression of VCAM-1. A more general goal is to identify selective compounds and methods for suppressing the expression of redox sensitive genes or activating redox sensitive genes that are suppressed. An even more general goal is to identify selective compounds, pharmaceutical compositions and methods of using the compounds for the treatment of inflammatory diseases. It is therefore an object of the present invention to provide new compounds for the treatment of disorders mediated by VCAM-1. It is also an object to provide new pharmaceutical compositions for the treatment of diseases and disorders mediated by the expression of VCAM-1. It is a further object of the invention to provide compounds, compositions, and methods of treating disorders and diseases mediated by VCAM-1, including cardiovascular and inflammatory diseases. Another object of the invention is to provide compounds, compositions, and method of treating cardiovascular and inflammatory diseases. It is another object of the invention to provide compounds, compositions and methods to treat arthritis. Another object of the invention is to provide compounds, compositions and methods to treat rheumatoid arthritis. The inventions compounds, compositions and methods are also suitable as disease modifying anti-rheumatoid arthritis drugs (DMARDs). It is yet another object of the invention to provide compounds, compositions and methods to treat asthma. It is another object of the invention to provide compounds, methods and compositions to inhibit the progression of atherosclerosis. It is still another object of the invention to provide compounds, compositions, and methods to treat or prevent transplant rejection. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of lupus. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of inflammatory bowel disease. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of autoimmune diabetes. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of multiple sclerosis. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of diabetic retinopathy. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of diabetic nephropathy. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of diabetic vasculopathy. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of rhinitis. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of ischemia-reperfusion injury. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of post-angioplasty restenosis. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of chronic obstructive pulmonary disease (COPD). It is a further object of the present invention to provide compounds, methods and compositions for the treatment of glomerulonephritis. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of Graves disease. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of gastrointestinal allergies. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of conjunctivitis. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of dermatitis. It is a further object of the present invention to provide compounds, methods and compositions for the treatment of psoriasis. SUMMARY OF THE INVENTION It has been discovered that particular chalcone derivatives inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorders that are mediated by VCAM-1 include, but are not limited to arthritis, asthma, dermatitis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, diabetic nephropathy, diabetic vasculopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. The compounds disclosed herein can also be used in the treatment of inflammatory skin diseases that are mediated by VCAM-1, as well as human endothelial disorders that are mediated by VCAM-1, which include, but are not limited to psoriasis, dermatitis, including eczematous dermatitis, Kaposi's sarcoma, multiple sclerosis, as well as proliferative disorders of smooth muscle cells. In yet another embodiment, the compounds disclosed herein can be selected to treat anti-inflammatory conditions that are mediated by mononuclear leucocytes. In one embodiment, the compounds of the present invention are selected for the prevention or treatment of tissue or organ transplant rejection. Treatment and prevention of organ or tissue transplant rejection includes, but is not limited to treatment of recipients of heart, lung, combined heart-lung, liver, kidney, pancreatic, skin, spleen, small bowel, or corneal transplants. The compounds can also be used in the prevention or treatment of graft-versus-host disease, such as sometimes occurs following bone marrow transplantation. In an alternative embodiment, the compounds described herein are useful in both the primary and adjunctive medical treatment of cardiovascular disease. The compounds are used in primary treatment of, for example, coronary disease states including atherosclerosis, post-angioplasty restenosis, coronary artery diseases and angina. The compounds can be administered to treat small vessel disease that is not treatable by surgery or angioplasty, or other vessel disease in which surgery is not an option. The compounds can also be used to stabilize patients prior to revascularization therapy. Compounds of the present invention are of the formula or its pharmaceutically acceptable salt or ester, wherein the substituents are defined herein. DETAILED DESCRIPTION OF THE INVENTION It has been discovered that compounds of the invention inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. These compounds can be administered to a host as monotherapy, or if desired, in combination with another compound of the invention or another biologically active agent, as described in more detail below. In a 1st embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group, consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 2β , R 3β , R 4β , R 5β or R 6β , or one of R 2α , R 3α , R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl; and/or wherein when one of R 2β , R 3β , R 4β , R 5β or R 6β is a carbon-carbon linked heterocyclic or heteroaryl, only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or wherein when one of R 2α , R 3α , R 4α , R 5α or R 6α is a carbon-carbon linked heterocyclic or heteroaryl, only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and/or at least one of R 2α , R 3α , R 4α , R 5α , R 6α or one of R 2β , R 3β , R 4β , R 5β , R 6β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 2 nd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 2β , R 3β , R 4β , R 5β or R 6β , or one of R 2α , R 3α , R 4α , R 5α or R 6α must be carbon-carbon linked heterocyclic or heteroaryl; and/or wherein when one of R 2β , R 3β , R 4β , R 5β or R 6β is a carbon-carbon linked heterocyclic or heteroaryl, only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or wherein when one of R 2α , R 3α , R 4α , R 5α or R 6α is a carbon-carbon linked heterocyclic or heteroaryl, only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and/or at least one of R 2α , R 3α , R 4α , or one of R 2β , R 3β , R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR, —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 3 rd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N( 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 2β , R 3β , R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and/or at least one of R 2α , R 3α , R 4α , R 5α , or R 6α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 4th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N( 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and/or at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , —SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 5th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N( 2 ) 2 . In a 6th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 7th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In an 8th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1) 2 C(O)NR 7 R 8 , amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , oxo, cyano, —C(O)NR 7 R 8 , and —(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 9th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, heterocyclicamino lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, dialkylamino, N(R 2 ) 2 , —NR 7 R 8 , tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 8-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 10th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, lower alkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, heteroaryl lower alkoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, carboxy, —C(O)OR 2 , —C(O)N(R 2 ) 2 , and —C(O)NR 7 R 8 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, hydroxy, hydroxyalkyl, heterocyclic, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, and lower alkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 5- to 7-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from carboxy or —C(O)OR 2 ; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In an 11th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, and carboxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy. In a 12th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy. In a 13th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heteroaryl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy. In a 14th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, fluorine, chlorine, methoxy, ethoxy, propoxy, 3-(1-morpholino) propoxy, 2-(1-morpholino) ethoxy, CH 3 O(CH 2 ) 2 O(CH 2 ) 2 —, wherein one of R 4β , R 5β or R 6β must be selected from the group consisting of thiophen-s-yl, thiophen-3-yl, benzo[b]thiophen-2-yl, benzo[b]thiophen-3-yl, indol-2-yl, indol-3-yl, pyrrol-2-yl, pyrrol-3-yl, 1-methyl-indol-2-yl, 1-methyl-indol-3-yl, N-Boc-indol-2-yl, N-Boc-indol-3-yl, N-Boc-pyrrol-2′yl, and N-Boc-pyrrol-3-yl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy. In a 15th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, methoxy, 3-(1-morpholino) propoxy, 2-(1-morpholino) ethoxy, and CH 3 O(CH 2 ) 2 O(CH 2 ) 2 ; wherein one of R 4β , R 5β or R 6β must be selected from the group consisting of thiophen-s-yl, benzo[b]thiophen-2-yl, indol-2-yl, 1-methyl-indol-2-yl, N-Boc-indol-2-yl, N-Boc-pyrrol-2′yl, and N-Boc-pyrrol-3-yl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy. In a 16 th embodiment, the invention is selected from a compound A compound selected from the group consisting of 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid;4-[3E-(4-Pyrimidin-5-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(4-Thiazol-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;2-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid;4-[3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;2-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid, sodium salt;4-[3E-(4-Thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3-{4-(thien-2-yl)-phenyl}-3-oxo-E-propenyl]-benzoic acid, sodium salt;4-[3-{4-(thien-2-yl)-phenyl}-3-oxo-E-propenyl]-benzoic acid;4-[3-(2-Methoxy-4-thiophen-2-yl-phenyl)-3-oxo-E-propenyl]-benzoic acid;4-[3E-(4-Pyrrolidin-1-yl-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-{4-Fluoro-3-(thiophen-2-yl)-phenyl}-acryloyl]-benzoic acid;4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid;4-[3E-(2-Fluoro-4-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(2,4-Dimethoxy-5-pyrimidin-5-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(2-Cyclopropylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-{3E-[5-(3,5-Dimethyl-isoxazol-4-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid;4-[3E-(4-Methoxy-2-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;2-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;2-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-indole-1-carboxylic acid tert-butyl ester;4-[3E-(2,6-Dimethoxy-4-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-{3E-[5-(2,4-Dimethoxy-pyrimidin-5-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid;4-[3E-(2,4-Dimethoxy-6-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-{3E-[2,4-Dimethoxy-5-(5-methyl-thiophen-2-yl)-phenyl]-acryloyl}-benzoic acid;4-[3E-(4-Methoxy-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(3-Thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;3-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(3-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid;4-[3E-(2-Methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(2,4-Dimethoxy-5-pyrazin-2-yl-phenyl)-acryloyl]-benzoic acid;4-{3E-[4-(1-Carboxy-1-methyl-ethoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;2-[3E-(4-Methoxy-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-(3E-{2-Methoxy-4-[2-(2-methoxy-ethoxy)-ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic acid;4-{3E-[4-(3-Hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;5-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid methyl ester;5-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid;4-[3E-(4-Ethoxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(4-Hydroxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(2,4-Dimethoxy-5-thiazol-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid, sodium salt;2-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-pyrrole-1-carboxylic acid tert-butyl ester;4-[3E-(2-Hydroxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-{3E-[2-(1-Carboxy-1-methyl-ethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride;2 4-{3E-[5-(1H-Indol-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid;4-{3E-[2-(3,5-Dimethyl-isoxazol-4-ylmethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;4-[3E-(2-Pyrrolidin-1-yl-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-{3E-[2-(3-Hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;4-{3E-[2-(3-Morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride;4-{3E-[4-Methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride;4-[3E-(2-Dimethylcarbamoylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-[3E-(4-Methoxy-2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-{3E-[2,4-Dimethoxy-5-(2-methyl-thiazol-4-yl)-phenyl]-acryloyl}-benzoic acid;4-{3E-[5-(1H-Benzoimidazol-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid;4-[3E-(2-Carbamoylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-2-oxo-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;4-(3E-{4-Methoxy-2-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic acid, hydrochloride;4-{3E-[2,4-Dimethoxy-5-(1H-pyrazol-4-yl)-phenyl]-acryloyl}-benzoic acid;4-{3E-[2,4-Dimethoxy-5-(2H-tetrazol-5-yl)-phenyl]-acryloyl}-benzoic acid;4-{3E-[5-(3H-Imidazo[4,5-b]pyridin-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid;2-{4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-2-methyl-propionic acid;4-{3E-[5-(2-Cyclopropyl-1H-imidazol-4-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid, hydrochloride;4-{3E-[5-(4-Isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid;4-{3E-[2,4-Dimethoxy-5-(1-methyl-1H-indol-2-yl)-phenyl]-acryloyl}-benzoic acid; and4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid ethyl ester, or its pharmaceutically acceptable salt or ester. In a 17 th embodiment, the invention is a compound selected from the group consisting of 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid;4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid; and4-{3E-[4-Methoxy-2-(2-morpholin-4-y-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride, or its pharmaceutically acceptable salt or ester. In an 18th embodiment, the invention is 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid or its pharmaceutically acceptable salt or ester. In a 19 th embodiment, the invention is 4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid, or its pharmaceutically acceptable salt or ester. In a 20 th embodiment, the invention is 4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid; and, or its pharmaceutically acceptable salt or ester. In a 21st embodiment, the invention is 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride, or its pharmaceutically acceptable salt or ester. In a 22 nd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy. In a 23rd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , and R 6α are independently selected from the group consisting of hydrogen and carboxy; R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked tetrahydrofuran-2-yl or dihydrofuran-2-yl; with the proviso that at least one of R 2α , R 3α , or R 4α must be carboxy. In a 24th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 1 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 25th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino-NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , and —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 26th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , and —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3,4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 27th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, heterocyclicamino lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, dialkylamino, N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , and —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 8-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 28 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, lower alkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, heteroaryl lower alkoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —N(R 2 )C(O)R 2 , —C(O)NH 2 , and —C(O)NHR 2 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, akenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, and lower alkyl which may be optionally substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, heteroaryl, and heterocyclic, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 5- to 7-membered monocyclic ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, heterocyclic, amino, aminoalkyl, and —NR 7 R 8 . In a 29th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, —N(R 2 )C(O)R 2 , —C(O)NH 2 , and —C(O)NHR 2 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is hydrogen; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of heterocyclic, amino, aminoalkyl, and —NR 7 R 8 . In a 30th embodiment, the invention is represented by the following compounds: 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-N-(2-morpholin-4-yl-ethyl)-benzamide;4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-N-(2,2,2-trifluoro-ethyl)-benzamide;4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzamide;4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamide;4-{3E-[4-Methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzamide;N-Acetyl-4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamide; and4-[3E-(5-Benzo[b]thiophen -2-yl-2,4-dimethoxy-phenyl)-acryloyl]-N-isobutyryl-benzamide. In a 31 st embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 32nd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NH 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 33 rd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH—SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, arylarylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 34th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, heterocyclicamino lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, dialkylamino, N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —SCH 2 C(O)OH—SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , and —C(O)NHSO 2 R 2 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 8-membered monocyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 35th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, lower alkyl, alkenyl, alkynyl, carbocycle, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, heteroaryl lower alkoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —N(R 2 )C(O)R 2 , —SCH 2 C(O)OH—SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , and —C(O)NHSO 2 R 2 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen and lower alkyl, which may be optionally substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl and lower alkyl, which may be substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 5- to 7-membered monocyclic ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , and —SO 2 NHC(O)R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 36 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, alkenyl, alkynyl, carbocycle, heteroaryl, heterocyclic, hydroxyl, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, —N(R 2 )C(O)R 2 , —SO 2 NH 2 , —SO 2 NHR 2 , SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , and —C(O)NHSO 2 R 2 , all of which can be optionally substituted by one or more selected from the group consisting of alkenyl, acyl, hydroxy, hydroxyalkyl, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is hydrogen; R 2 is lower; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —SC(R 1 ) 2 C(O)OR 2 , —SO 2 NH 2 , —SO 2 NR 7 R 8 , and —SO 2 NHC(O)R 2 . In a 37 th embodiment, the invention is represented by the following compound: 4-[3E-(4-Thiophen-2-yl-phenyl)-acryloyl]-benzenesulfonamide;4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzenesulfonamide;4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide;2-{5-Methoxy-2-[3-oxo-3-(4-sulfamoyl-phenyl)-E-propenyl]-4-thiophen-2-yl-phenoxy}-2-methyl-propionic acid;2-{2,4-Dimethoxy-5-[3-oxo-3-(4-sulfamoyl-phenyl)-E-propenyl]-phenyl}-indole-1-carboxylic acid tert-butyl ester;4-{3E-[5-(1H-Indol-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide;4-{3E-[4-Methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide;4-{3E[2-(3-Hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide;4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-N-isobutyryl-benzenesulfonamide;4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}benzenesulfonamide, hydrochloride;4-{3E-[4-Methoxy-2-(1H-tetrazol-5-ylmethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide;4-[3E-(2,4-Dimethoxy-5-pyridin-3-yl-phenyl)-acryloyl]-benzenesulfonamide;4-{3E-[4-(3-Hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide;4-{3E-[5-(4-Isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide;4-{3E-[5-(2-Cyclopropyl-1H-imidazol-4-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide;4-{3E-[5-(3H-Imidazo[4,5-b]pyridin-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide;4-{3E-[2-(1H-Benzoimidazol-2-ylmethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide;4-{3E-[4-Methoxy-2-(pyridin-2-ylmethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide;4-{3E-[2-(Benzotriazol-1-ylmethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide; and4-{3E-[2,4-Dimethoxy-5-(1-methyl-1H-indol-2-yl)-phenyl]-acryloyl}-benzenesulfonamide. In a 38th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 39 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl optionally substituted by alkoxycarbonyl. R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of amino, —N(C(O)NHR 2 ) 2 , NR 2 SO 2 R 2 and —NR 2 SO 2 R 2 ; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 40th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 41st embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is hydrogen or lower alkyl optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; with the proviso that at least one of R 2α , R 3α , or R 4α must be selected from —OC(R 1 ) 2 C(O)OH; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 42 nd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —C(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 1 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; and/or At least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 43 rd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently alkyl or lower alkyl; R 7 and R 8 are independently selected from the group consisting of alkyl, linked together forming a 6-membered monocyclic ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or R 3α and R 4α taken together or R 4α and R 5α taken together, or R 3β and R 4β taken together or R 4β and R 5β taken together form a heterocyclic ring optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, or hydroxyalkyl groups. In a 44 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl , arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 C(O)OH; and/or at least one of R 2α , R 3α , or R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 , wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 45 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently alkyl or lower alkyl; R 7 and R 8 are independently selected from the group consisting of alkyl, linked together forming a 6-membered monocyclic ring; wherein one of R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or R 3α and R 4α taken together or R 4α and R 5α taken together or R 3β and R 4β taken together or R 4β and R 5β taken together form a 5-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of alkyl, lower alkyl, cycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxycarbonyl; provided that R 2α , R 3α , R 4α , R 5α , R 6α , R 2β , R 3β , R 4β , R 5β and R 6β cannot be —OC(R 1 ) 2 COOH. In a 46th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 2α , R 3α , R 4α , R 5α or R 6α , or one of R 2β , R 3β , R 4β , R 5β or R 6β must be a carbon-carbon linked heterocyclic or heteroaryl; and/or wherein when one of R 2α , R 3α , R 4α , R 5α or R 6α is a carbon-carbon linked heterocyclic or heteroaryl, only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and/or wherein when one of R 2β , R 3β , R 4β , R 5β or R 6β is a carbon-carbon linked heterocyclic or heteroaryl, only one of R 2α , R 3α , R 4α , R 5α or R 6α can be —OCH 3 ; and/or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together, or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; and/or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α cannot be —OC(R 1 ) 2 C(O)OH; and/or at least one of R 2β , R 3β , R 4β , or one of R 2α , R 3α , R 4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 47th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 2α , R 3α , R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together, or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α cannot be —OC(R 1 ) 2 C(O)OH; and with the proviso that at least one of R 2β , R 3β , R 4β , R 5β , or R 6β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 48th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α , or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together, or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α cannot be —OC(R 1 ) 2 C(O)OH; and with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 N 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 49th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —(O)N(R 2 ) 2 . In a 50th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 51st embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In an 52 nd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, polyol-alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, (CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 53 rd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, heterocyclicamino lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, dialkylamino, N(R 2 ) 2 , —NR 7 R 8 , tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 8-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 54th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, lower alkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, heteroaryl lower alkoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, carboxy, —C(O)OR 2 , —C(O)N(R 2 ) 2 , and —C(O)NR 7 R 8 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, hydroxy, hydroxyalkyl, heterocyclic, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, and lower alkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 5- to 7-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from carboxy or —C(O)OR 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 55th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, and carboxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be carboxy. In a 56th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , and R 6β are independently selected from the group consisting of hydrogen and carboxy; R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl; with the proviso that at least one of R 2β , R 3β , or R 4β must be carboxy. In a 57th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , and R 6β are independently selected from the group consisting of hydrogen and carboxy; R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heteroaryl; with the proviso that at least one of R 2β , R 3β , or R 4β must be carboxy. In a 58th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , and R 6β are independently selected from the group consisting of hydrogen and carboxy; R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, fluorine, chlorine, methoxy, ethoxy, propoxy, 3-(1-morpholino) propoxy, 2-(1-morpholino) ethoxy, CH 3 O(CH 2 ) 2 O(CH 2 ) 2 —, wherein one of R 4α , R 5α or R 6α must be selected from the group consisting of thiophen-s-yl, thiophen-3-yl, benzo[b]thiophen-2-yl, benzo[b]thiophen-3-yl, indol-2-yl, indol-3-yl, pyrrol-2-yl, pyrrol-3-yl, 1-methyl-indol-2-yl, 1-methyl-indol-3-yl, N-Boc-indol-2-yl, N-Boc-indol-3-yl, N-Boc-pyrrol-2′yl, and N-Boc-pyrrol-3-yl; with the proviso that at least one of R 2β , R 3β , or R 4β must be carboxy. In a 59th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , and R 6β are independently selected from the group consisting of hydrogen and carboxy; R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, methoxy, 3-(1-morpholino) propoxy, 2-(1-morpholino) ethoxy, and CH 3 O(CH 2 ) 2 O(CH 2 ) 2 ; wherein one of R 4α , R 5α or R 6α must be selected from the group consisting of thiophen-s-yl, benzo[b]thiophen-2-yl, indol-2-yl, 1-methyl-indol-2-yl, N-Boc-indol-2-yl, N-Boc-pyrrol-2′yl, and N-Boc-pyrrol-3-yl; with the proviso that at least one of R 2β , R 3β , or R 4β must be carboxy. In a 60th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , and R 6β are independently selected from the group consisting of hydrogen and carboxy; R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic; with the proviso that at least one of R 2β , R 3β , or R 4β must be carboxy. In a 23rd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , and R 6β are independently selected from the group consisting of hydrogen and carboxy; R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked tetrahydrofuran-2-yl or dihydrofuran-2-yl; with the proviso that at least one of R 2β , R 3β , or R 4β must be carboxy. Embodiment 6c. Amide Branch In a 61st embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)N 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 62nd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino-NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , and —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, (lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 63 rd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , and —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 64th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, heterocyclicamino lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, dialkylamino, N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , and —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 8-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 65 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, lower alkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, heteroaryl lower alkoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —N(R 2 )C(O)R 2 , —C(O)NH 2 , and —C(O)NHR 2 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, and lower alkyl which may be optionally substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, heteroaryl, and heterocyclic, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 5- to 7-membered monocyclic ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, heterocyclic, amino, aminoalkyl, and —NR 7 R 8 . In a 66th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, —N(R 2 )C(O)R 2 , —C(O)NH 2 , and —C(O)NHR 2 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is hydrogen; R 2 is lower alkyl; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —C(O)NH 2 , —C(O)NHR 2 , —C(O)NHC(O)R 2 , and —C(O)NHSO 2 R 2 ; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of heterocyclic, amino, aminoalkyl, and —NR 7 R 8 . In a 67th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 68th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N( 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 69th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH—SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , cyano, tetrazol-5-yl, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, and —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, arylarylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 70th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, heterocyclicamino lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, dialkylamino, N(R 2 ) 2 , —NR 7 R 8 , —N(R 2 )C(O)R 2 , —SCH 2 C(O)OH —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , and —C(O)NHSO 2 R 2 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 8-membered monocyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 71st embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, lower alkyl, alkenyl, alkynyl, carbocycle, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, heteroaryl lower alkoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —N(R 2 )C(O)R 2 , —SCH 2 C(O)OH—SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , and —C(O)NHSO 2 R 2 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen and lower alkyl, which may be optionally substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl and lower alkyl, which may be substituted by one or more selected from the group consisting of halo, lower alkyl, —NR 7 R 8 , alkoxy, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 5- to 7-membered monocyclic ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , and —SO 2 NHC(O)R 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, —NR 7 R 8 , —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 72nd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, alkenyl, alkynyl, carbocycle, heteroaryl, heterocyclic, hydroxyl, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, —N(R 2 )C(O)R 2 , —SO 2 NH 2 , —SO 2 NHR 2 , SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , and —C(O)NHSO 2 R 2 , all of which can be optionally substituted by one or more selected from the group consisting of alkenyl, acyl, hydroxy, hydroxyalkyl, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is hydrogen; R 2 is lower; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —SC(R 1 ) 2 C(O)OR 2 , —SO 2 NH 2 , —SO 2 NR 7 R 8 , and —SO 2 NHC(O)R 2 . In a 73rd embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 74 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl optionally substituted by alkoxycarbonyl. R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of amino, —N(C(O)NHR 2 ) 2 , NR 2 SO 2 R 2 and —NR 2 SO 2 R 2 ; wherein all R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 75th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 76th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is hydrogen or lower alkyl optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is lower alkyl optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently alkyl, and linked together forming a 6-membered monocyclic ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; with the proviso that at least one of R 2β , R 3β , or R 4β must be selected from —OC(R 1 ) 2 C(O)OH; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 77th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and/or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together, or R 2α and R 3α taken together R 3α and R 4α taken together or R 4α and R 5α taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR 7 R 8 , and halo; and/or at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 ; wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 78th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, (O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently alkyl or lower alkyl; R 7 and R 8 are independently selected from the group consisting of alkyl, linked together forming a 6-membered monocyclic ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and/or R 3β and R 4β taken together or R 4β and R 5β taken together, or R 3α and R 4α taken together or R 4α and R 5α taken together form a heterocyclic ring optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, or hydroxyalkyl groups. In a 79 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O) 2 -lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R 2 , R 2 C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH 2 ) 2 ) 1-3 —O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR 2 , N(R 2 ) 2 , —NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , —NHC(O)N(R 2 ) 2 , thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, —SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 R 2 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO 2 H 2 , —PO 3 H 2 , —P(R 2 )O 2 H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; R 7 and R 8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and/or R 2β and R 3β taken together or R 3β and R 4β taken together or R 4β and R 5β taken together or R 2α and R 3α taken together or R 3α and R 4α taken together or R 4α and R 5α taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 ; provided that R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α cannot be —OC(R 1 ) 2 C(O)OH; and/or at least one of R 2β , R 3β , or R 4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR 2 , —C(O)NH 2 , —C(O)NHR 2 , —C(O)N(R 2 ) 2 , —C(O)NR 7 R 8 , —C(O)NHC(O)NHR 2 , —C(O)NHC(O)N(R 2 ) 2 , —C(O)NHC(O)NR 7 R 8 , —C(O)NHSO 2 NHR 2 , —C(O)NHSO 2 N(R 2 ), —C(O)NHSO 2 NR 7 R 8 , —C(O)NHC(O)R 2 , —C(O)NHSO 2 R 2 , —C(CH 3 ) 2 C(O)OH, —(CH 2 ) y C(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R 1 ) 2 C(O)OH, —SC(R 1 ) 2 C(O)OR 2 , —SCH 2 C(O)OH, ——SCF 2 C(O)OH, —SO 2 NH 2 , —SO 2 NHR 2 , —SO 2 N(R 2 ) 2 , SO 2 NR 7 R 8 , —SO 2 NHC(O)R 2 , —SR 2 , —SO 2 NHC(O)NHR 2 , —SO 2 NHC(O)N(R 2 ) 2 , —SO 2 NHC(O)NR 7 R 8 , —OC(R 1 ) 2 C(O)OH, —OC(R 1 ) 2 C(O)OR 2 , —OC(R 1 ) 2 C(O)NH 2 , —OC(R 1 ) 2 C(O)NHR 2 , —OC(R 1 ) 2 C(O)N(R 2 ) 2 , —OC(R 1 ) 2 C(O)NR 7 R 8 , amino, —NHR 2 , N(R 2 ) 2 , NR 7 R 8 , —NHC(R 1 ) 2 C(O)OH, —NHC(R 1 ) 2 C(O)OR 2 , —NHC(O)R 2 , —N(R 2 )C(O)R 2 , —NHC(O)OR 2 , —NHC(O)SR 2 , —NHSO 2 NHR 2 , —NHSO 2 R 2 , —NHSO 2 NR 7 R 8 , —N(C(O)NHR 2 ) 2 , —NR 2 SO 2 R 2 , —NHC(O)NHR 2 , —NHC(O)NR 7 R 8 , and —NHC(O)N(R 2 ) 2 , wherein all R 1 , R 2 , R 7 and R 8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —C(O)N(R 2 ) 2 . In a 80 th embodiment, the invention is represented by Formula I or its pharmaceutically acceptable salt or ester, wherein: R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, (O(CH 2 ) 2 ) 1-3 —O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR 7 R 8 , alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR 7 R 8 , and —(O)N(R 2 ) 2 ; R 2 is independently alkyl or lower alkyl; R 7 and R 8 are independently selected from the group consisting of alkyl, linked together forming a 6-membered monocyclic ring; wherein one of R 4α , R 5α or R 6α must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R 2β , R 3β , R 4β , R 5β or R 6β can be —OCH 3 ; and/or R 3β and R 4β taken together or R 4β and R 5β taken together or R 3α and R 4α taken together or R 4α and R 5α taken together form a 5-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of alkyl, lower alkyl, cycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxycarbonyl; provided that R 2β , R 3β , R 4β , R 5β , R 6β , R 2α , R 3α , R 4α , R 5α and R 6α cannot be —OC(R 1 ) 2 COOH. As an 81 st embodiment, the invention is a pharmaceutical composition comprising any of the above 80 embodiments or any of the specific Examples below together with one or more pharmaceutically acceptable carriers. An 82 nd embodiment includes embodiments 1–80 above or any of the Examples as a means to treat or prophylactically treat an inflammatory disorder including arthritis, rheumatoid arthritis, asthma, diabetic retinopathy, diabetic nephropathy, diabetic vasculopathy, multiple sclerosis, allergic rhinitis, chronic obstructive pulmonary disease, systemic lupus erthematosus, atherosclerosis, and restinosis. A further embodiment includes the intermediates used to make the final compounds of the invention. Said intermediates are useful as starting materials for making the compounds of the invention as well as having pharmaceutical activity alone. Another embodiment of the invention includes the process for making both the intermediates as well as the final compounds. Definitions A wavy line used as a bond“ ”, denotes a bond which can be either the E- or Z-geometric isomer. When not used as a bond, the wavy line indicates the point of attachment of the particular substituent. The terms “alkyl” or “alk”, alone or in combination, unless otherwise specified, refers to a saturated straight or branched primary, secondary, or tertiary hydrocarbon from 1 to 10 carbon atoms, including, but not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, and sec-butyl. The term “lower alkyl” alone or in combination refers to an alkyl having from 1 to 4 carbon atoms. The alkyl group may be optionally substituted with any moiety that does not otherwise interfere with the reaction or that provides an improvement in the process, including but not limited to but limited to halo, haloalkyl, hydroxyl, carboxyl, acyl, aryl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrozine, carbamate, phosphonic acid, phosphonate, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene et al., Protective Groups in Organic Synthesis , John Wiley & Sons, Second Edition, 1991, hereby incorporated by reference. Specifically included are CF 3 and CH 2 CF 3 . The term “alkenyl”, alone or in combination, means a non-cyclic alkyl of 2 to 10 carbon atoms having one or more unsaturated carbon-carbon bonds. The alkenyl group may be optionally substituted with any moiety that does not otherwise interfere with the reaction or that provides an improvement in the process, including but not limited to but limited to halo, haloalkyl, hydroxyl, carboxyl, acyl, aryl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrozine, carbamate, phosphonic acid, phosphonate, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene et al., Protective Groups in Organic Synthesis , John Wiley & Sons, Second Edition, 1991, hereby incorporated by reference. Specifically included are CF 3 and CH 2 CF 3 . The term “alkynyl”, alone or in combination, means a non-cyclic alkyl of 2 to 10 carbon atoms having one or more triple carbon-carbon bonds, including but not limited to ethynyl and propynyl. The alkynyl group may be optionally substituted with any moiety that does not otherwise interfere with the reaction or that provides an improvement in the process, including but not limited to but limited to halo, haloalkyl, hydroxyl, carboxyl, acyl, aryl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrozine, carbamate, phosphonic acid, phosphonate, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene et al., Protective Groups in Organic Synthesis , John Wiley & Sons, Second Edition, 1991, hereby incorporated by reference. Specifically included are CF 3 and CH 2 CF 3 . The terms “carboxy”, “COOH” and “C(O)OH” are used interchangeably. The terms “alkoxycarbonyl” and “carboalkoxy” are used interchangeably. Used alone or in combination, the terms mean refer to the radical —C(O)OR, wherein R is alkyl as defined herein. The term “thio”, alone or in combination, means the radical —S—. The term “thiol”, alone or in combination, means the radical —SH. The term “hydroxy”, alone or in combination means the radical —OH. The term “sulfonyl”, alone or in combination means the radical —S(O) 2 —. The term “oxo” refers to an oxygen attached by a double bond (═O). The term “carbocycle”, alone or in combination, means any stable 3- to 7-membered monocyclic or bicyclic or 7- to 14-membered bicyclic or tricyclic or an up to 26-membered polycyclic carbon ring, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocyles include, but are not limited to, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, biphenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin). The term “cycloalkyl”, alone or in combination, means a saturated or partially unsaturated cyclic alkyl, having from 1 to 10 carbon atoms, including but not limited to mono- or bi-cyclic ring systems such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexenyl, and cyclohexyl. The term “aryl”, alone or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such rings may be attached together in a pendent manner or may be fused. The aryl group can be optionally substituted with one or more of the moieties selected from the group consisting of alkyl, alkenyl, alkynyl, heteroaryl, heterocyclic, carbocycle, alkoxy, oxo, aryloxy, arylalkoxy, cycloalkyl, tetrazolyl, heteroaryloxy; heteroarylalkoxy, carbohydrate, amino acid, amino acid esters, amino acid amides, alditol, halogen, haloalkylthi, haloalkoxy, haloalkyl, hydroxyl, carboxyl, acyl, acyloxy, amino, aminoalkyl, aminoacyl, amido, alkylamino, dialkylamino, arylamino, nitro, cyano, thiol, imide, sulfonic acid, sulfate, sulfonate, sulfonyl, alkylsulfonyl, aminosulfonyl, alkylsulfonylamino, haloalkylsulfonyl, sulfanyl, sulfinyl, sulfamoyl, carboxylic ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, thioester, thioether, oxime, hydrazine, carbamate, phosphonic acid, phosphate, phosphonate, phosphinate, sulfonamido, carboxamido, hydroxamic acid, sulfonylimide or any other desired functional group that does not inhibit the pharmacological activity of this compound, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene, et al., “Protective Groups in Organic Synthesis”, John Wiley and Sons, Second Edition, 1999. In addition, adjacent groups on an aryl ring may combine to form a 5- to 7-membered saturated or partially unsaturated carbocyclic, aryl, heteroaryl or heterocyclic ring, which in turn may be substituted as above. The term “heterocyclic”, alone or in combination, refers to a nonaromatic cyclic group that may be partially (containing at least one double bond) or fully saturated and wherein the ring contains at least one heteroatom selected from oxygen, sulfur, nitrogen, or phosphorus. The terms “heteroaryl” or “heteroaromatic”, alone or in combination, refer to an aromatic ring containing at least one heteroatom selected from sulfur, oxygen, nitrogen or phosphorus. The heteroaryl or heterocyclic ring may optionally be substituted by one or more substituent listed as optional substituents for aryl. In addition, adjacent groups on the heteroaryl or heterocyclic ring may combine to form a 5- to 7-membered carbocyclic, aryl, heteroaryl or heterocyclic ring, which in turn may be substituted as above. Nonlimiting examples of heterocylics and heteroaromatics are pyrrolidinyl, tetrahydrofuryl, tetrahydrofuranyl, pyranyl, purinyl, tetrahydropyranyl, piperazinyl, piperidinyl, morpholino, thiomorpholino, tetrahydropyranyl, imidazolyl, pyrolinyl, pyrazolinyl, indolinyl, dioxolanyl, or 1,4-dioxanyl. aziridinyl, furyl, furanyl, pyridyl, pyridinyl, pyridazinyl, pyrimidinyl, benzoxazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazole, indazolyl, triazinayl, 1,3,5-triazinyl, thienyl, isothiazolyl, imidazolyl, tetrazolyl, pyrazinyl, benzofuranyl, quinolyl, isoquinolyl, benzothienyl, isobenzofuryl, pyrazolyl, indolyl, isoindolyl, benzimidazolyl, purinyl, carbazolyl, oxazolyl, thiazolyl, benzothiazolyl, isothiazolyl, 1,2,4-thiadiazolyl, isooxazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, pyrrolyl, quinazolinyl, quinoxalinyl, benzoxazolyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, xanthinyl, hypoxanthinyl, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,3-oxadiazole, thiazine, pyridazine, triazolopyridinyl or pteridinyl wherein said heteroaryl or heterocyclic group can be optionally substituted with one or more substituent selected from the same substituents as set out above for aryl groups. Functional oxygen and nitrogen groups on the heteroaryl group can be protected as necessary or desired. Suitable protecting groups can include trimethylsilyl, dimethylhexylsilyl, t-butyldimethylsilyl, and t-butyldiphenylsilyl, trityl or substituted trityl, alkyl groups, acyl groups such as acetyl and propionyl, methanesulfonyl, and p-toluenesulfonyl. The term “thienyl”, alone or in combination, refers to a five member cyclic group wherein the ring contains one sulfur atom and two double bonds. The term “benzothienyl”, alone or in combination, refers to a five member cyclic group wherein the ring contains one sulfur atom and two double bonds fused to a phenyl ring. The term “aryloxy”, alone or in combination, refers to an aryl group bound to the molecule through an oxygen atom. The term “heteroaryloxy”, alone or in combination, refers to a heteroaryl group bound to the molecule through an oxygen atom. The term “aralkoxy”, alone or in combination, refers to an aryl group attached to an alkyl group which is attached to the molecule through an oxygen atom. The term “heterocyclearalkoxy” refers to a heterocyclic group attached to an aryl group attached to an alkyl-O-group. The heterocyclic, aryl and alkyl groups can be optionally substituted as described above. The terms “halo” and “halogen”, alone or in combination, refer to chloro, bromo, iodo and fluoro. The terms “alkoxy” or “alkylthio”, alone or in combination, refers to an alkyl group as defined above bonded through an oxygen linkage (—O—) or a sulfur linkage (—S—), respectively. The terms “lower alkoxy” or “lower alkylthio”, alone or in combination, refers to a lower alkyl group as defined above bonded through an oxygen linkage (—O—) or a sulfur linkage (—S—), respectively. The term “acyl”, alone or in combination, refers to a group of the formula C(O)R′, wherein R′ is an alkyl, aryl, alkaryl or aralkyl group, or substituted alkyl, aryl, aralkyl or alkaryl, wherein these groups are as defined above. The term “acetyl”, alone or in combination, refers to the radical —C(O)CH 3 . The term “amino”, alone or in combination, denotes the radical —NH 2 or —NH—. The term “nitro”, alone or in combination, denotes the radical —NO 2 . The term “substituted”, means that one or more hydrogen on the designated atom or substituent is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and the that the substitution results in a stable compound. When a subsitutent is “oxo” (keto) (i.e., ═O), then 2 hydrogens on the atom are replaced. The term “alditol”, as referred to herein, and unless otherwise specified, refers to a carbohydrate in which the aldehyde or ketone group has been reduced to an alcohol moiety. The alditols of the present invention can also be optionally substituted or deoxygenated at one or more positions. Exemplary substituents include hydrogen, halo, haloalkyl, carboxyl, acyl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, amino acid, amino acid esters and amides, phosphonyl, phosphinyl, phosphoryl, thioester, thioether, oxime, hydrazine, carbamate, phosphonic acid, and phosphonate,. Particular exemplary substituents include amine and halo, particularly fluorine. The substituent or alditol can be either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene, et al., Protective Groups in Organic Synthesis , John Wiley and Sons, Second Edition, 1999, hereby incorporated by reference. The alditol may have 3, 4, 5, 6 or 7 carbons. Examples of useful alditols are those derived from reduction of monosaccharides, including specifically those derived from the reduction of pyranose and furanose sugars. The term “carbohydrate”, as referred to herein, and unless otherwise specified, refers to a compound of carbon, hydrogen and oxygen that contains an aldehyde or ketone group in combination with at least two hydroxyl groups. The carbohydrates of the present invention can also be optionally substituted or deoxygenated at one or more positions. Carbohydrates thus include substituted and unsubstituted monosaccharides, disaccharides, oligosaccharides, and polysaccharides. The saccharide can be an aldose or ketose, and may comprise 3, 4, 5, 6, or 7 carbons. In one embodiment the carbohydrates are monosaccharides. In another embodiment the carbohydrates are pyranose and furanose sugars. As used herein, the term “patient” refers to warm-blooded animals or mammals, and in particular humans, who are in need of the therapy described herein. The term “host”, as used herein, refers to a unicellular or multicellular organism, including cell lines and animals, and preferably a human. Synthesis of the Active Compounds The compounds of the present invention can be readily prepared by those skilled in the art of organic synthesis using commonly known methods, many of which are described by J, March, in Advanced Organic Chemistry, 4 th Edition (Wiley Interscience, New York, 1992) and D. N. Dnar in The Chemistry of Chalcones and Related Compounds (Wiley-Interscience, New York, 1981), incorporated herein by reference. Compounds of the present invention are prepared either by reacting a heteroaryl- or heterocyclic-substituted aryl or heteroaryl ketone with a suitably substituted aryl aldehyde or by reacting a suitably substituted aryl ketone with a heteroaryl- or heterocyclic-substituted aryl or heteroaryl aldehyde. This reaction, which is a condensation reaction, is suitably carried out under base- or acid-catalyzed conditions. The reaction may be suitably carried out in water or protic organic solvents such as lower alcohols (e.g. methanol, ethanol, tert-butanol), lower carboxylic acid (e.g. formic acid, glacial acetic acid, propionic acid), or in aprotic organic solvents such as ethers (e.g. tetrahydrofuran, dioxane, diethyl ether), liquid amides (e.g. dimethylformamide, hexamethylphosphordiamide), dimethylsulfoxide, or hydrocarbons (e.g. toluene, benzene), or mixtures of such solvents. When carrying out the reaction under basic conditions, the base may be selected from sodium, lithium, potassium, barium, calcium, magnesium, aluminum, ammonium, or quarternary ammonium hydroxides, lower alkoxides (e.g. methoxides, ethoxides, tert-butoxides), carbonates, borates, oxides, hydrides, or amides of lower secondary amines (e.g. diisopropyl amides, methylphenyl amides). Primary aromatic amines such as aniline, free secondary amines such as dimethyl amine, diethyl amine, piperidine, or pyrrolidine, tertiary amines such as pyridine, as well as basic ion exchange resins may also be used. Alternatively, a phase-transfer catalyst such as cetyl trimethyl ammonium chloride can also be used to facilitate the reaction, particularly when water is the solvent. Alternatively, the aldol condensation reaction can also be carried out in an aprotic solvent such as tetrahydrofuran (THF) with an organic base. The preferred solvent is THF and the preferred base is lithium diisopropylamide (LDA). In this manner an aldol reaction may take place first and the subsequent dehydration reaction may take place during an aqueous workup. Acid catalysts may be selected from hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, sulfonic acids (such as paratoluenesulfonic or methansulfonic acid), lower carboxylic acid (such as formic, acetic, or propionic acid), lower halogenated carboxylic acid (such as trifluoroacetic acid), Lewis acids (such as BF 3 , POCl 3 , PCl 5 , FeCl 3 ), or acid ion exchange resins. The reaction may be carried out at temperatures in the range of −80° C. to +150° C., preferably in the range of 0° C. to +100° C., and more preferably at room temperature. The time of reaction may be from 30 minutes to approximately 24 hours. Compounds of the invention may be isolated as either mixtures of cis (Z) and trans (E) geometric isomers or either pure trans (E) isomers. If desired, either the mixtures or the pure trans isomers may be isomerized to the corresponding predominantly cis (Z) iomers using methods well known in the literature. In the above reactions, it may be preferred or necessary to protect various sensitive or reactive groups present in the starting materials so as to prevent said groups from interfering with the reactions. Such protection may be carried out in a well-known manner as taught by Theodora W. Green and Peter G. M. Wuts, in Protective Groups in Organic Chemistry Third Edition (Wiley, 1999) or using methods from references cited therein or of the like. The protecting group may be removed after the reaction in a manner known per se. The following schemes will prove useful to those skilled in the art in manufacturing the compounds of the invention: Legend for all Schemes: 1. R, R′, R″, R′″, and R″″ can be any substitution including H;2. R, R′, R″, R′″, and R″″ can be suitably functionalized;3. R, R′, R″, R′″, and R″″ can represent multiple substitutions;4. Two adjacent R, R′, R″, R′″, or R″″ can form a ring;5. Dashed double bond can be at any location of a ring;6. Y, Y′, Y″, and Y′″ independently represent N(H), O, or S,7. X and X′ independently represent Cl, Br, or I;8. Each R, R′, R″, R′″, R″″, Y, Y′, Y″, Y′″, X or X′ is independent in each scheme;9. HetAr represents suitably substituted heterocyclic aryl;10. Cy represents cyclohexyl. EXAMPLES The following examples are understood to be illustrative only and are not intended to limit the scope of the present invention in any way. All intermediates and final products have been completely characterized by conventional proton NMR, mass spectral analyses and standard analytical methods known to those skilled in the art. Example 1 1-(2,2-Bis-hydroxymethyl-benzo[1,3]dioxol-5-yl)-3E-(3,4-dimethoxy-5-thiophen-2-yl-phenyl)-propenone Ex-1A: Catechol (2.2 g, 20 mmol) was dissolved in acetone. Diethyl dibromomalonate (7.0 g, 22 mmol) and potassium carbonate (2.76 g) were added, and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and water was added to the residue. The residue was extracted with dichloromethane, and the organic phase was washed with brine, dried over magnesium sulfate and evaporated. Chromatography (hexanes/ethyl acetate, 4:1) gave 3.9 g of benzo[1,3]dioxole-2,2-dicarboxylic acid diethyl ester. 1 H-NMR (CDCl 3 ) δ 6.90–6.97 (m, 4H), 4.37 (q, J=7 Hz, 4H), 1.32 (t, J=7 Hz, 6H). Ex-1B: [Bis(ethoxycarbonyl)methyldenedioxy]benzene obtained from Ex-1A (3.9 g, 14.7 mmol) was dissolved in THF (100 mL) and cooled with ice-water. Lithium aluminum hydride (1 M solution in THF, 44 mL) was added dropwise, and the mixture was stirred overnight. The reaction was carefully quenched with saturated sodium sulfate until there was no further bubbling. The mixture was stirred overnight, then filtered, and the filtrate was dried over magnesium sulfate. Chromatography (dichloromethane/methanol, 10:1) gave 0.5 g of the desired (2-hydroxymethyl-benzo[1,3]dioxol-2-yl)-methanol. 1 H-NMR (CDCl 3 ) δ 6.82 (s, 4H), 3.94 (d, J=7 Hz, 4H), 1.98 (t, J=7 Hz, 2H). Ex-1C: Aluminum chloride (1.3 g) was added to nitromethane followed by the addition of acetyl chloride (1.86 g). Then (2-hydroxymethyl-benzo[1,3]dioxol-2-yl)-methanol obtained from Ex-1B (0.5 g) in nitromethane was added dropwise. The mixture was stirred overnight. Water was added to the reaction mixture, and it was extracted with dichloromethane. The organic phase was washed with brine, dried over magnesium sulfate and evaporated. Chromatography gave 0.28 g of 5-acetyl-benzo[1,3]dioxole-2,2-dicarboxylic acid diethyl ester. 1 H-NMR (CDCl 3 ) δ 7.56 (d, J=7 Hz, 1H), 7.43 (s, 1H), 6.85 (d, J=7 Hz, 1H), 4.42 (s, 4H), 2.53 (s, 3H), 2.05 (s, 6H). Ex-1D: A solution of 5-bromo-3,4-dimethoxybenzaldehyde (10.23 g, 41.7 mmol) in 359 mL of ethylene glycol dimethyl ether was purged with nitrogen gas for 30 min. The solution was treated with tetrakis(triphenylphosphine)palladium(0) (5.0 g, 4.3 mmol), thiophene-2-boronic acid (8.01 g, 62.6 mmol), and a solution of 2 N sodium carbonate 72 mL, 3.45 mmol). The reaction was refluxed for 16 h. The reaction mixture was concentrated, diluted with an aqueous solution of saturated sodium bicarbonate (75 mL), and extracted with dichloromethane (2×100 mL). The organic layer was dried over sodium sulfate and concentrated to a brown solid. The crude material was purified by silica gel chromatography (1:1 ethyl acetate/hexanes) to give 9.42 g (90%) of the desired 3,4-dimethoxy-5-(thien-2-yl)benzaldehyde product. 1 H-NMR (300 MHz, CDCl 3 ) δ 9.94 (s, 1H), 7.79 (d, 1H), 7.57 (dd, 1H), 7.41 (d, 1H), 7.36 (d, 1H), 7.13 (dd, 1H), 3.97 (s, 3H), 3.93 (s, 3H). 5-Acetyl-benzo[1,3]dioxole-2,2-dicarboxylic acid diethyl ester obtained from Ex-1C (0.28 g, 1.11 mmol) and 3,4-dimethoxy-5-(thien-2-yl)benzaldehyde obtained from Ex-1D (0.275 g, 1.11 mmol) were dissolved in ethanol, and 50% sodium hydroxide solution (0.4 mL) was added. The mixture was stirred at room temperature overnight. Most of the solvent was removed under reduced pressure, and water was added to the remainder. The resulting product was extracted with dichloromethane. The organic phase was dried over magnesium sulfate and evaporated. Chromatography gave 0.19 g (38%) of the title compound as a yellow solid, m.p. 74–80° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 7.74 (d, 1H), 7.63 (dd, 1H), 7.49–7.55 (m, 3H), 7.38 (d, 1H), 7.37 (d, 1H), 7.12 (dd, 1H), 7.07 (d, 1H), 6.88 (d, 1H), 3.99 (s, 4H), 3.99 (s, 4H), 3.98 (s, 3H), 3.88 (s, 3H). Anal. Calculated for C 24 H 22 O 7 S: C, 63.42; H, 4.88; S, 7.06; found: C, 63.46; H, 5.11; S, 6.55. Example 2 1-(2,2-Bis-hydroxymethyl-benzo[1,3]dioxol-5-yl)-3E-(4-thiophen-2-yl-phenyl)-propenone Ex-2A: 4-(Thien-2-yl)benzaldehyde was obtained in a similar manner as described in Ex-1D from 4-bromobenzaldehyde. 1 H-NMR (CDCl 3 ) δ 10.00 (s, 1H), 7.88 (d, J=9 Hz, 2H), 7.77 (d, J=9 Hz, 2H), 7.46 (d, J=4 Hz, 1H), 7.39–7.41 (m, 1H), 7.12–7.15 (m, 1H). The title compound was obtained when 5-acetyl-benzo[1,3]dioxole-2,2-dicarboxylic acid diethyl ester from Ex-1C was condensed with 4-(Thien-2-yl)benzaldehyde from Ex-2A in a similar manner as described in Ex-1. Yellow solid, mp 166–168° C., 23.6% yield. 1 H-NMR (CDCl 3 ) δ 7.77 (d, J=15 Hz, 1H), 7.60–7.65 (m, 5H), 7.51 (d, J=2 Hz, 1H), 7.45 (d, J=15 Hz, 1H), 7.37–7.38 (m, 1H), 7.32 (d, J=5 Hz, 1H), 7.09 (dd, J=4, 5 Hz, 1H), 6.88 (d, J=8 Hz, 1H), 3.96 (d, J=7 Hz, 4H). MS m/z=394 ([M] + , 50%), 363 (100%). HRMS (EI) Calcd. for C 22 H 18 O 5 S: 394.0875. Found: 394.0869. Example 3 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid Ex-3A: A sample of 5-bromo-2,4-dimethoxybenzaldehyde (4.9 g, 20.0 mmol) was dissolved in ethylene glycol dimethyl ether (50 mL). Tetrakis(triphenylphosphine)palladium(0) (2.32 g, 2 mmol) was added, and the mixture was stirred at room temperature under nitrogen for 5 min. Benzo[b]thiophene-2-boronic acid (4.27 g, 24 mmol) and sodium carbonate solution (2 M, 20 mL) were added. The mixture was stirred at reflux under nitrogen for 24 hours. Upon cooling to room temperature, the mixture was poured into water and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and evaporated. Silica gel chromatography (hexane/ethyl acetate 2:1 then 1:1) gave 4.75 g (83%) of the desired 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde. 1 H NMR (CDCl 3 ) δ 10.36 (s, 1H), 8.20 (s, 1H), 7.83–7.78 (m, 2H), 7.68 (s, 1H), 7.36–7.27 (m, 2H), 6.54 (s, 1H), 4.06 (s, 3H), 4.00 (s, 3H). An alternative procedure: 5-bromo-2,4-dimethoxybenzaldehyde (20 g), benzo[b]thiophene-2-boronic acid (16 g) and THF (200 mL) were sequentially charged into a clean reaction vessel fitted with a reflux condenser, mechanical stirrer and nitrogen inlet adapter. Nitrogen was bubbled into the resulting solution for 20 min followed by the sequential addition of KF (10 g), and Pd( t Bu 3 P) 2 (0.417 g). The solution was immediately heated to 60° C. and aged for 1.5 h. (Note: The HPLC assay at this point routinely indicated complete consumption of 5-bromo-2,4-dimethoxybenzaldehyde, <0.5 area % of benzo[b]thiophene-2-boronic acid along with 0.5 area % of an unknown (0.55 RRT). These impurities are removed during crystallization.) Upon completion, as determined by HPLC, the reaction was diluted with H 2 O (200 mL) and transferred to a separatory funnel containing EtOAc (200 mL) and H 2 O (200 mL). The layers were cut and the aqueous layer was extracted with EtOAc (100 mL). The combined organic cuts were filtered through a pre-washed pad of solka floc (5 g). The pad of solka floc and spent catalyst were washed with fresh EtOAc (200 mL) and this wash combined with the batch. The resultant filtrate was batch concentrated and solvent switched to 33 wt % 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde in THF in preparation for crystallization. (Note: The internal temperature during batch concentration should be kept above 45° C. to prevent premature crystallization.) The resulting THF solution of 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde was then charged with heptane (20 mL) and slowly cooled to ambient temperature. Crystallization was then completed with the slow addition of heptane (175 mL) and cooling to 4° C. After aging for 1 h, the batch was filtered and then dried on the filter funnel under a stream of N 2 . The semi-wet cake was then transferred to clean trays and dried to a constant weight in the vacuum oven (40° C., 20 inHg) affording 23.74 g (97% yield) of desired 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde as a light orange crystalline solid, m.p. 134–136° C. HPLC assay of this solid indicated >99.9 LCAP. 1 H-NMR identical as above. To a solution of 4-acetylbenzoic acid (1.50 g, 9.1 mmol) and 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde from Ex-3A (3.27 g, 11.0 mmol) in N,N-dimethylformamide (76 mL) was added a solution of sodium hydroxide (5 M, 7.3 mL, 36.5 mmol). The reaction mixture was allowed to stir at room temperature for 2 h and was then diluted with water to a volume of 150 mL. The solution was washed with dichloromethane and acidified with concentrated sulfuric acid to pH=3. The resulting solution was then extracted with dichloromethane. The dichloromethane extract was washed with brine, dried over sodium sulfate and concentrated. The resulting oily product solidified in ethanol. The solid was further stirred in ethanol for one day and collected by filtration. The solid was washed with ethanol, then dried in vacuo to afford the title compound as a yellow solid (2.2 g, 54%). 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.36 (s, 1H), 8.21 (d, 2H), 8.07 (m, 3H), 7.93 (m, 3H), 7.82 (d, 1H), 7.32 (m, 2H), 6.86 (s, 1H), 4.08 (s, 3H), 4.00 (s, 3H). Anal. Calculated for C 26 H 20 O 5 S·1/6H 2 O: C, 69.78; H, 4.58; S, 7.17; found: C, 69.95; H, 4.69; S, 7.15. HPLC purity: 97.9% (area percentage). An alternative procedure: 5-(Benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde from Ex-3A (42.3 g), 4-acetylbenzoic acid (22.1 g), MeOH (250 mL) and DMF (600 mL) were sequentially charged into a clean reaction vessel fitted with a mechanical stirrer and nitrogen inlet adapter. After complete dissolution, LiOMe (10.5 g) was added in one portion and the resulting solution was aged at 40° C. for 2 h. Upon completion, as determined by HPLC, the reaction mixture was transferred to a separatory funnel containing cold H 2 O (800 mL, precooled to 10 deg C.). An additional 400 mL cold H 2 O was used to rinse the reaction vessel and this rinse was also added to the seperatory funnel. The combined aqueous was washed with iPrOAc (500 mL) and then acidified to a pH of 3 with 6 N HCl (ca. 60 mL). The resulting heterogeneous solution was aged for 30 min and then the precipitate was filtered, washed with 70% EtOH (100 mL) and dried on the filter funnel under a stream of N 2 affording desired acid 5 as a crude yellow solid. The crude dry product and THF (260 mL) were charged into a clean reaction vessel fitted with a mechanical stirrer and nitrogen inlet adapter. Heptane (30 mL) was slowly added to the resulting solution over 30 min and then aged resulting in crystallization. Additional heptane (270 mL) was added over 1 h, aged for an additional 1 h and then filtered. The reaction vessel was then rinsed with 70% EtOH (100 mL) and this rinse was added to the filter cake. The wet cake was then transferred to a clean reaction vessel containing 70% EtOH (750 mL) and the resulting heterogeneous mixture was stirred overnight. The product was then filtered, rinsed with fresh 70% EtOH (100 mL) and then dried on the filter funnel under a stream of N 2 . The semi-wet cake was then transferred to clean trays and dried to a constant weight in the vacuum oven (40° C., 20 inHg) affording 52.05 g (87% yield) of desired 4-[3-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-E-acryloyl]-benzoic acid 5 as a yellow crystalline solid, m.p. 231–232° C. (dec.). HPLC assay of this solid indicated >99.9 LCAP. 1 H-NMR identical as above. Example 4 4-[3E-(4-Pyrimidin-5-yl-phenyl)-acryloyl]-benzoic acid Ex-4A: 4-Pyrimidin-5-yl-benzaldehyde was obtained pyrimidine-5-boronic acid and 4-bromobenzaldehyde in a similar manner as described in Ex-3A, 88.6% yield. 1 H-NMR (CDCl 3 ) δ 10.11 (s, 1H), 9.28 (s, 1H), 9.01 (s, 2H), 8.05 (d, J=8 Hz, 2H), 7.77 (d, J=8 Hz, 2H). The title compound was obtained in a similar manner as described in Ex-3 from 4-pyrimidin-5-yl-benzaldehyde (Ex-4A) and 4-acetylbenzoic acid. Yellow solid, mp>260° C., 45% yield. 1 H-NMR (DMSO-d 6 ) δ 9.21 (s, 2H), 9.19 (s, 1H), 8.24 (d, J=9 Hz, 2H), 8.01–8.09 (m, 5H), 7.9 (d, J=6 Hz, 2H), 7.81 (d, J=15 Hz, H), MS m/z=330 ([M] + , 100%). HRMS (EI) Calcd. for C 20 H 14 N 2 O 3 : 330.1004. Found: 330.1000. Example 5 4-[3E-(4-Thiazol-2-yl-phenyl)acryloyl]-benzoic acid Ex-5A: 4-Thiazol-2-yl-benzaldehyde was prepared from 4-bromobenzaldehyde and thiazole-2-boronic acid in a similar manner as described in Ex-3A, 82% yield. 1 H-NMR (CDCl 3 ) δ 10.07 (s, 1H), 8.15 (d, J=8 Hz, 2H), 7.95–7.98 (m, 3H), 7.45 (d, J=3 Hz, 1H). HMRS (EI) calcd. for C 10 H 7 NOS: 189.0248; found: 189.0242. The title compound was obtained in a similar manner as described in Ex-3 from 4-thiazol-2-yl-benzaldehyde (Ex-5A) and 4-acetylbenzoic acid. Yellow solid, mp 232–235° C., 20% yield. 1 H-NMR (CDCl 3 ) δ 8.24 (d, J=9 Hz, 2H), 8.11 (d, J=9 Hz, 2H), 8.05 (d, J=9 Hz 2H), 7.93 (d, J=3 Hz, 1H), 7.86 (d, J=15 Hz, 1H), 7.74 (d, J=9 Hz, 2H), 7.57 (d, J=15 Hz, 1H), 7.41 (d, J=3 Hz, 1H), MS m/z=335 ([M] + , 100%). HRMS (EI) Calcd. for C 19 H 13 NO 3 S: 335.0616. Found: 335.0618. Example 6 4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-6A: 5-bromo-2,4-dimethoxybenzaldehyde (20.3 g), thiophene-2-boronic acid (11.6 g) and THF (200 mL) were sequentially charged into a clean reaction vessel fitted with a reflux condenser, mechanical stirrer and nitrogen inlet adapter. Nitrogen was bubbled into the resulting solution for 20 min followed by the sequential addition of KF (10.1 g), and Pd( t Bu 3 P) 2 (0.424 g). The solution was immediately heated to 60° C. and aged for 1.5 h. The reaction was diluted with H 2 O (200 mL) and transferred to a separatory funnel containing EtOAc (200 mL) and H 2 O (200 mL). The layers were cut and the aqueous layer was extracted with EtOAc (100 mL). The combined organic cuts were filtered through a pre-washed pad of solka floc (5 g). The pad of solka floc and spent catalyst were washed with fresh EtOAc (200 mL) and this wash combined with the batch. The resultant filtrate was concentrated to dryness. The crude product was dissolved in THF (38 mL) and crystallized upon heptane (152 mL) addition. The product was filtered and then dried to a constant weight in the vacuum oven (38° C., 20 inHg) affording 19.32 g (94% yield) of desired 2,4-dimethoxy-5-thiophen-2-yl-benzaldehyde as a light off-white solid, m.p. 125–126° C. 1 H-NMR (300 MHz, CDCl 3 ): 10.34 (s, 1H), 8.12 (s, 1H), 7.44 (dd, 1H, J=3.5 and 1.5 Hz), 7.31 (dd, 1H, J=5.2 and 1.5 Hz), 7.07 (dd, 1H, J=5.2 and 3.5 Hz), 6.51 (s, 1H), 4.02 (s, 3H), 3.99 (s, 3H). 2,4-Dimethoxy-5-thiophen-2-yl-benzaldehyde from Ex-6A (7.81 g), 4-acetylbenzoic acid (4.9 g), MeOH (60 mL) and DMF (150 mL) were sequentially charged into a clean reaction vessel fitted with a stir bar and nitrogen inlet adapter. After complete dissolution LiOMe (4.60 g) was added and the resulting solution was aged for 5 h. The reaction was diluted with H 2 O (200 mL) and transferred to a separatory funnel containing iPrOAc (100 mL). The layers were cut and the aqueous layer was acidified to a pH of 1 with 3 N HCl. The resulting precipitate was filtered and then dried on the filter funnel under a stream of N 2 . The crude product was then dissolved in THF (60 mL) and crystallized with the addition of heptane (60 mL). The product was filtered and then dried to a constant weight in the vacuum oven affording 8.9 g (75% yield) of the title compound as a yellow solid, m.p. 213–216° C. 1 H-NMR (300 MHz, CDCl 3 ): 8.20 (d, 2H, J=8.5 Hz), 8.09 (d, 1H, J=16.1 Hz), 8.06 (d, 2H, J=8.5 Hz), 7.85 (s, 1H), 7.52 (d, 1H, J=16.1 Hz), 7.40 (m, 1H), 7.30 (dd, 1H, J=5.2 and 1.7 Hz), 7.08 (dd, 1H, J=5.2 and 3.6 Hz), 6.53 (s, 1H), 3.98 (s, 3H), 3.97 (s, 3H); EIMS m/z=394 (M + ). Anal. calc. for C 22 H 18 O 5 S: C, 66.99; H, 4.60; S, 8.13; found: C, 66.71; H, 4.59; S, 8.10. Example 7 2-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid The title compound was obtained starting from 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde from Ex-3A and 2-acetylbenzoinc acid in a similar manner as described in Ex-3. Yellow solid, mp 220–223° C. (dec.). 1 H-NMR (DMSO-d 6 ) δ 8.01 (s, 1H), 7.88 (d, J=7.3 Hz, 1H), 7.80–7.75 (m, 2H), 7.45–7.24 (m, 7H), 7.11 (d, J=1H), 6.79 (s, 1H), 4.00 (s, 3H), 3.88 (s, 3H). MS m/z=445 (M + , 100%). Example 8 4-[3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid The title compound was obtained in a similar manner as described in Ex-3 from 3,4-dimethoxy-5-(thien-2-yl)benzaldehyde (Ex-1D) and 4-acetylbenzoic acid. Yellow solid, mp 231° C. 1 H-NMR (DMSO-d 6 ) δ 8.23 (d, 2H), 8.08 (d, 2H), 7.96 (d, 1H), 7.90 (m, 1H), 7.77 (m, 2H), 7.59 (d, 1H), 7.54 (m, 1H), 7.13 (dd, J=4, 4 Hz, 1H). MS m/z=395 ([M+H] + , 100%). Example 9 2-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid, sodium salt To a solution of 2-acetyl-benzoic acid (0.75 g, 4.6 mmol) and 5-benzo[b]thiophen-2-yl-2,4-dimethoxy-benzaldehyde (Ex-3A, 1.64 g, 5.5 mmol) in N,N-dimethylformamide (38 mL) was added sodium hydroxide (5M, 3.7 mL, 18.5 mmol). The reaction mixture was allowed to stir for 2 hours at ambient temperature and was diluted with water (50 mL) and sodium carbonate (2M, 20 mL). The aqueous solution was extracted with dichloromethane. A yellow precipitate formed in dichloromethane and was collected by filtration, washed with dichloromethane, dried in vacuo to give the title compound as a yellow solid (1.53 g, 67%), mp 214–217° C. (dec). 1 H-NMR (DMSO-d 6 ) δ 7.93–7.87 (m, 3H), 7.77 (d, J=8.0 Hz, 2H), 7.33–7.26 (m, 4H), 7.09–7.06 (m, 2H), 7.01 (d, J=17.0 Hz, 1H), 6.78 (s, 1H), 3.99 (s, 3H), 3.88 (s, 3H). MS m/z=467 ([M+Na] + , 75%), 445 ([M+H] + , 100%). Anal. (C 26 H 19 O 5 SNa.1.3H 2 O) Calc. C, 63.55; H, 4.35; S, 6.52; found C, 63.74; H, 4.44; S, 6.55. Example 10 4-[3E-(4-Thiophen-2-yl-phenyl)-acryloyl]-benzoic acid The title compound was obtained by condensing 4-(thien-2-yl)benzaldehyde from Ex-2A and 4-acetylbezoic acid in a similar manner as described in Ex-3. Yellow solid, 56% yield, mp>260° C. 1 H-NMR (DMSO-d 6 ) δ 8.01–8.08 (m, 4H), 7.72 (d, J=8 Hz, 2H), 7.68 (s, 2H), 7.61 (d, J=8 Hz, 2H), 7.41 (d, J=4 Hz, 1H), 7.35 (d, J=4 Hz, 1H), 7.04 (dd, J=4, 8 Hz, 1H). MS m/z=334 ([M+Na] + , 100%). Anal. (C 22 H 14 O 3 S) Calc. C, 71.84; H, 4.22; S, 9.59; found C, 71.44; H, 4.32; S, 9.43. Example 11 1-(4-Amino-phenyl)-3E-(3,4-dimethoxy-5-thiophen-2-yl-phenyl)-propenone A suspension of 3,4-dimethoxy-5-(thien-2-yl)benzaldehyde (1.8 g, 7.4 mmol) from Ex-1D in an aqueous solution of 5 N potassium hydroxide (37 mL) was treated with cetyltrimethyl ammonium chloride (39 mL, 29.6 mmol) and 4-aminoacetophenone (1.0 g, 7.4 mmol). The reaction was stirred for 16 h at room temperature. The reaction mixture was titrated with 6 M H 2 SO 4 to a pH of 7. The mixture was extracted with dichloromethane (2×75 mL). The organic layer was washed with aqueous NaHCO 3 (2×25 mL), brine, dried over sodium sulfate, and concentrated to a yellow foam. The crude material was purified by silica gel chromatography (1:1 ethyl acetate and hexanes) to give 720.0 mg (27%) of the title compound as a yellow solid, mp. 67–71° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 7.94 (d, 2H), 7.75 (d, 1H), 7.54 (s, 1H), 7.53 (s, 1H), 7.46 (d, 1H), 7.39 (d, 1H), 7.13 (d, 1H), 7.11 (m, 1H), 6.72 (d, 2H), 4.16 (s, 2H), 3.97 (s, 3H), 3.87 (s, 3H). Anal. calculated for C 21 H 19 NO 3 S·1/5H 2 O: C, 68.60; H, 5.28; S, 8.72; found C, 68.51; H, 5.40, S, 8.69. MS (Pos. Ion ES): calcd for C 21 H 20 NO 3 S, m/z=366 [M+H] + , found: m/z=366 [M+H] + . Example 12 1-(4-Amino-phenyl)-3E-(4-thiophen-2-yl-phenyl)-propenone The title compound was prepared from 4-(thien-2-yl)benzaldehyde (Ex-2A) and 4-aminoacetophenone in a similar manner as described in Ex-11. Yellow solid, 45% yield, mp 185–187° C. 1 H-NMR (CDCl 3 ) δ 7.95 (d, 2H), 7.79 (d, 1H), 7.65 (m, 4H), 7.55 (d, 1H), 7.39 (d, 1H), 7.33 (dd,J=5, 5 Hz, 1H), 7.11 (dd, J=5, 5 Hz, 1H), 6.71 (d, 2H), 4.16 (s, 2H). MS m/z=305 ([M] + , 100%). Anal. calculated for C 19 H 15 NOS: C, 74.72; H, 4.95; S, 10.50; found C, 74.60; H, 5.05; S, 10.42. Example 13 1-(4-Amino-phenyl)-3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-propenone The title compound was prepared from 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde (Ex-3A) and 4-aminoacetophenone in a similar manner as described in Ex-11. Yellow solid, 24% yield, mp 98–104° C. 1 H-NMR (CDCl 3 ) δ 8.10 (d, 1H), 7.95 (m, 3H), 7.82 (m, 2H), 7.67 (s, 1H), 7.60 (d, 1H), 7.32 (dd, J=8.8 Hz, 2H), 6.71 (d, 2H), 6.57 (s, 1H), 4.11 (br s, 2H), 4.02 (s, 3H), 3.99 (s, 3H). MS m/z=415 ([M] + , 39%), 384 (100%). Anal. calculated for C 25 H 21 NO 3 S.1/3H 2 O: C, 71.24; H, 5.18; S, 7.61; found C, 71.63; H, 5.18; S, 7.55. Example 14 N-{4-[3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-methanesulfonamide Ex-14A: A solution of 1-(4-amino-phenyl)-3E-(3,4-dimethoxy-5-thiophen-2-yl-phenyl)-propenone (Ex-11, 472.2 mg, 1.3 mmol) and triethylamine (398.63 μL, 2.86 mmol) was stirred in 20 mL of anhydrous dichloromethane. The mixture was treated with mesyl chloride (100 μL, 1.3 mmol). The reaction mixture was stirred for 16 hours and heated gently for another 4 hours. The crude material was purified by silica gel chromatography (1:3 ethyl acetate/hexane) to give 337.0 mg (quantitative) of 1-[4-bis-(methanesulfonyl)aminophenyl]-3E-[(3,4-dimethoxy-5-(thien-2-yl)phenyl]-propenone. 1 H-NMR (300 MHz, CDCl 3 ) δ 8.06 (d, 2H), 7.76 (d, 1H), 7.53 (m, 2H), 7.49 (d, 2H), 7.38 (m, 1H), 7.36 (d, 1H), 7.10 (m, 1H), 7.08 (m, 1H), 3.94 (s, 3H), 3.86 (s, 3H), 3.42 (s, 6H). A solution of 1-[4-bis-(methanesulfonyl)aminophenyl]-3E-[(3,4-dimethoxy-5-(thien-2-yl)phenyl]-propenone (378.86 mg, 0.73 mmol) from Ex-14A in tetrahydrofuran (6.6 mL) was treated with aqueous 1N NaOH (1.4 mL, 1.4 mmol). The reaction was stirred at room temperature for 1 h. The reaction was titrated with 1 N HCl to a pH of 6. The crude material was purified by silica gel chromatography (5% MeOH/CH 2 Cl 2 with 1% acetic acid) to give 269.2 mg (83%) of the title compound as a solid, 83% yield, mp. 71–75° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 8.04 (d, 2H), 7.76 (d, 1H), 7.52 (m, 2H), 7.40 (d, 1H), 7.37 (m, 1H), 7.29 (d, 2H), 7.10 (m, 1H), 7.08 (m, 1H), 3.95 (s, 3H), 3.86 (s, 3H), 3.12 (s, 1H), 3.09 (s, 3H). MS (Pos. Ion ES): calcd for C 22 H 22 NO 5 S 2 : m/z=444 [M+H] + , found: m/z=444 [M+H] + . HRMS m/z: calc. 444.0939, found 444.0953. Example 15 (3-{4-[3E-(4-Thiophen-2-yl-phenyl)-acryloyl]-phenyl}-ureido)-acetic acid ethyl ester A solution of 1-(4-amino-phenyl)-3-(4-thiophen-2-yl-phenyl)-propenone (Ex-12, 250 mg, 0.80 mmol) and isocyanato-acetic acid ethyl ester (105.7 mg, 0.80 mmol) in toluene (15 mL) was refluxed for 16 hours. The reaction mixture was cooled to room temperature and the crude product precipitated out of solution. The material was suctioned filtered and dried on hi-vac to give 280.2 mg (79%) of the title compound as a yellow solid, mp 209–212° C. 1 H-NMR (DMSO-d6) δ 9.29 (br s, 1H), 8.08 (d, 2H), 7.90 (m, 3H), 7.71 (d, 3H), 7.60 (m, 4H), 7.14 (t, 1H), 6.61 (t, 1H), 4.09 (q, 2H), 3.86 (dd, J=2,6 Hz, 2H), 1.17 (t, 3H). MS m/z=435 ([M+H] + , 100%). HRMS m/z: calc. 435.1378, found 435.1375. Example 16 (3-[Ethoxycarbonylmethylaminocarbonyl]-3-{4-[3E-(3,4-dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-ureido)-acetic acid ethyl ester A solution of 1-(4-aminophenyl)-3E-[(3,4-dimethoxy-5-(thien-2-yl)phenyl]-propenone (Ex-11, 500 mg, 1.37 mmol) and ethyl isocyanatoacetate (177 mg, 1.37 mmol) in anhydrous methylene chloride (20 mL) was stirred at room temperature for 5 hours. Due to no reaction, the reaction mixture was concentrated, diluted with toluene (20 mL), treated with ethyl isocyanatoacetate (177 mg, 1.37 mmol), and refluxed for 14 hours. The reaction was concentrated, diluted with methylene chloride (50 mL), and washed with water (3×50 mL). The organic portion was collected, dried over sodium sulfate, and concentrated over silica gel. The crude material was purified by silica gel chromatography (50–75% ethyl acetate/hexanes) to give 178.0 mg (21%) of the title compound as a yellow solid, mp 83–86° C. 1 H-NMR (CDCl 3 ) δ 8.09 (d, 2H), 7.76 (d, 1H), 7.55 (m, 2H), 7.65 (d, 2H), 7.40 (m, 2H), 7.30 (m, 2H), 7.11 (m, 2H), 4.17 (q, 4H), 4.01 (d, 4H), 3.97 (s, 3H), 3.88 (s, 3H). MS m/z=646 ([M+Na] + , 100%). Anal. calculated for C 31 H 33 N 3 O 9 S: C, 59.70; H, 5.33; S, 5.14; found C, 60.18; H, 5.38; S, 5.17. Example 17 4-[3-{4-(thien-2-yl)-phenyl}-3-oxo-E-propenyl]-benzoic acid, sodium salt Ex-17A: 4′-Bromoacetophenone (3.98 g, 20 mmol) was dissolved in ethylene glycol dimethyl ether and then the solution was degassed with nitrogen for 15 minutes. Tetrakis(triphenylphosphine)palladium(0) (2.31 g, 2 mmol) was added, and the solution was further degassed for 10 minutes. Thiophene-2-boronic acid (3.07 g, 24 mmol) was added followed by the addition of sodium carbonate solution (2 M, 45 mL). The mixture was stirred at reflux under nitrogen overnight. Most of the solvent was removed, and water was added to the remainder. The solid was filtered out and recrystallized from ethanol and water to give 3.85 g of the desired 4′-(thien-2-yl)acetophenone as a solid, 95% yield. 1 H-NMR (CDCl 3 ) δ 7.97 (d, J=9 Hz, 2H), 7.70 (d, J=9 Hz, 2H), 7.44 (d, J=4 Hz, 1H), 7.38 (d, J=5 Hz, 1H), 7.11–7.14 (m, 1H), 2.62 (s, 3H). HMRS (EI) calcd. for C 12 H 10 OS: 202.0452; found: 202.0454. 4′-(Thien-2-yl)acetophenone obtained from Ex-17A (0.81 g, 4 mmol) and 4-carboxybenzaldehyde (0.6 g, 4 mmol) were dissolved in dimethylformamide (20 mL). Sodium hydroxide solution (5 M, 3.2 mL) was added over 30 minutes at room temperature, and the mixture was stirred for another 30 minutes at room temperature. The precipitate was filtered off and recrystallized from hot water to give the title compound as a yellow solid, 29% yield, m.p.>260° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.17 (d, 2H), 7.89 (d, 1H), 7.87 (d, 2H), 7.81 (d, 2H), 7.76 (d, 2H), 7.72 (d, 1H), 7.69 (d, 1H), 7.64 (d, 1H), 7.17 (dd, 1H). Anal. calculated for C 20 H 13 O 3 NaS.1/2H 2 O: C, 65.74; H, 3.86; S, 8.78; found: C, 65.66; H, 4.04; S, 9.04. Example 18 4-[3-{4-(thien-2-yl)-phenyl}-3-oxo-E-propenyl]-benzoic acid The title compound was prepared by acidifying its sodium salt from Ex-17. Yellow solid, mp 260–265° C., 67% yield. 1 H-NMR (DMSO-d 6 ) δ 8.18 (d, J=8 Hz, 2H), 8.00 (d, J=15 Hz, 1H), 7.91–7.94 (m, 4H), 7.82 (d, J=8 Hz, 2H), 7.77–7.79 (m, 1H), 7.71 (d, J=3 Hz, 1H), 7.66 (d, J=5 Hz, 1H), 7.16–7.19 (m, 1H), MS m/z=334 ([M] + , 100%). HRMS (EI) Calcd. for C 20 H 14 O 3 S: 334.0664. Found: 334.0669. Example 19 4-[3-(2-Methoxy-4-thiophen-2-yl-phenyl)-3-oxo-E-propenyl]-benzoic acid Ex-19A: 1-(2-Methoxy-4-thiophen-2-yl-phenyl)-ethanone was prepared from 4-iodo-2-methoxyacetophenone in a similar manner as described in Ex-17A. 1 H-NMR (CDCl 3 ) δ 7.53 (d, J=7 Hz, 1H), 7.37 (dd, J=2, 5 Hz, 1H), 7.06 (dd, J=4, 6 Hz, 1H), 6.98–7.00 (m, 1H), 6.88–6.95 (m, 2H), 3.84 (s, 3H), 2.10 (s, 3H). The title compound was prepared by condensing 1-(2-methoxy-4-thiophen-2-yl-phenyl)-ethanone (Ex-19A) and 4-carboxybenzaldehyde in a similar manner as described in Ex-17 except an acidic workup. Yellow solid, mp 193–195° C. 1 H-NMR (CDCl 3 ) □ 7.70 (d, J=8 Hz, 2H), 7.38 (d, J=8 Hz, 1H), 7.07–7.16 (m, 4H), 6.75–6.80 (m, 4H), 6.42 (d, J=16 Hz, 1H), 3.67 (s, 3H), MS m/z=364 ([M] + , 100%). Anal. Calculated for C 21 H 16 O 4 S: C, 69.21; H, 4.43; S, 8.80; found: C, 69.02; H, 4.56; S, 8.75. Example 20 4-[3E-(4-Pyrrolidin-1-yl-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-20A: A solution of 3-bromo-4-flouro-benzaldehyde (5.0 g, 24.6 mmol) and thiophene-2-boronic acid (4.7 g, 37.0 mmol) in ethylene glycol dimethyl ether (100 mL) was stirred at room temperature under nitrogen for 15 min. Then tetrakis(triphenylphosphine)-palladium(0) (2.8 g, 2.42 mmol) and a sodium carbonate solution (2 M, 33 mL) were added, and the resulting mixture was refluxed under nitrogen overnight. Upon cooling to room temperature the reaction was poured into water (100 mL) and extracted with ethyl acetate (2×100 mL). The organic phase was dried over magnesium sulfate, and the solvent was removed under reduced pressure. Silica gel chromatography (hexane/ethyl acetate, 1:1) gave 4.8 g (95%) of the desired 4-fluoro-3-(thiophen-2-yl)-benzaldehyde product as a yellow oil. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.0 (s, 1H), 8.18 (dd, 1H, J=7.3 and 2.4 Hz), 7.80 (m, 1H), 7.56 (dd, 1H, J=3.7 and 1.7 Hz), 7.44 (d, 1H, J=5.1 Hz), 7.36 (m, 1H), 7.16 (dd, 1H, J=5.1 and 3.7 Hz). Ex-20B: A solution of 4-fluoro-3-(thiophen-2-yl)-benzaldehyde (1.11 g, 5.38 mmol) from Ex-20A and pyrrolidine (13.0 g, 183.0 mmol) in dimethylformamide (30 mL) was treated with solid K 2 CO 3 (1.7 g, 12.3 mmol), and the resulting mixture was stirred at reflux for 1 week. Upon cooling to room temperature, the reaction was poured into water (100 mL) and extracted with ethyl acetate (2×100 mL). The organic phase was dried over magnesium sulfate, and the solvent was removed under reduced pressure. Silica gel chromatography (hexane/ethyl acetate, 2:1) gave 400 mg (29%) of the desired 4-pyrrolidin-1-yl-3-(thiophen-2-yl)-benzaldehyde product as a yellow oil. 1 H-NMR (300 MHz, CDCl 3 ) δ 9.75 (s, 1H), 7.71–7.74 (m, 2H), 7.30 (dd, 1H, J=5.1 and 1.6 Hz), 7.02 (dd, 1H, J=5.1 and 3.7 Hz), 6.96 (m, 1H), 6.81 (d, 1H, J=10.1 Hz), 3.15 (m, 4H), 1.84 (m, 4H). 4-Pyrrolidin-1-yl-3-(thiophen-2-yl)-benzaldehyde (400 mg, 1.55 mmol) from Ex-20B and 4-acetylbenzoic acid (255 mg, 1.55 mmol) were dissolved in dimethylformamide (30 mL). Sodium hydroxide solution (5 N, 1.25 mL) was added in one portion, and the mixture was stirred at room temperature overnight. The reaction was diluted with water (100 mL) and washed with ethyl acetate (100 mL). The aqueous phase was acidified with conc. HCl and extracted with ethyl acetate (2×100 mL). The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. Silica gel chromatography (100% ethyl acetate) followed by recrystallization from ethanol provided 80 mg (13%) of the title compound as a solid, m.p. 212–214° C. with decomposition. 1 H-NMR (300 MHz, CDCl 3 ) δ 8.21 (d, 2H, J=8.4 Hz), 7.06 (d, 2H, J=8.4 Hz), 7.80 (d, 1H, J=15.3 Hz), 7.58 (d, 1H, J=1.9 Hz), 7.52 (dd, 1H, J=8.5 and 1.9 Hz), 7.33 (m, 1H), 7.32 (d, 1H, 15.3 Hz), 7.01–7.06 (m, 2H), 6.82 (d, 1H, 7.9 Hz), 3.12 (m, 4H), 1.84 (m, 4H). MS m/z=403 ([M] + , 100%). HRMS (EI) Calcd. for C 24 H 21 NO 3 S: 403.1242. Found: 403.1251. Example 21 4-[3E-{4-Fluoro-3-(thiophen-2-yl)-phenyl}-acryloyl]-benzoic acid 4-Fluoro-3-thiophen-2-yl-benzaldehyde (1.0 g, 4.85 mmol, from Ex-20A) and 4-acetylbenzoic acid (0.80 g, 4.87 mmol) were dissolved in dimethylformamide (55 mL). Sodium hydroxide solution (5 N, 3.88 mL) was added in one portion, and the mixture was stirred at room temperature for 3 h. The reaction was diluted with water (100 mL) and washed with ethyl acetate (100 mL). The aqueous phase was acidified with conc. HCl and extracted with ethyl acetate (2×100 mL). The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. Recrystallization from ethanol provided 0.90 g (53%) of the title compound as a solid, m.p. 242–244° C. 1 H-NMR (300 MHz, d 6 -DMSO) δ 13.31 (bs, 1H), 8.32 (dd, 1H, J=8.2 and 2.0 Hz), 8.24 (d, 2H, J=8.2 Hz), 8.07 (d, 2H, J=7.9 Hz), 7.98 (d, 1H, J=16.1 Hz), 7.92 (m, 1H), 7.80 (d, 1H, J=16.1 Hz), 7.69–7.73 (m, 2H), 7.41 (dd, 1H, 10.8 and 9.2 Hz), 7.20 (m, 1H). MS m/z=352 ([M] + , 50%), 343 (100%). HRMS (EI) Calcd. for C 20 H 13 FO 3 S: 352.0569. Found: 352.0571. Example 22 1-(4-Mercapto-phenyl)-3E-(4-thiophen-2-yl-phenyl)-propenone To a solution of 4-mercaptoacetophenone (prepared according to European Patent Application 0271307) (0.57 g, 3.74 mmol) and 4-(thien-2-yl)-benzaldehyde (0.70 g, 3.74 mmol, Ex. 2A) in N,N-dimethylformamide (20 mL) was added a solution of sodium hydroxide (5 M, 3 mL). The solution was allowed to stir at room temperature for 3 h. The reaction mixture was then acidified with hydrochloric acid (0.5 M) to pH 3. The precipitate was collected by filtration, washed with water, and stirred in ethanol overnight. The resulting yellow solid was collected by filtration, washed with ethanol, and dried in vacuo to afford 0.68 g (56%) of the title compound as a solid, m.p.>110° C. (dec). MS (direct probe) m/z=322 (M + ). 1 H-NMR (CDCl 3 ) δ 7.98–8.01 (d, 1H), 7.90–7.93 (d, 1H), 7.79–7.84 (d, 2H), 7.61–7.66 (m, 3H), 7.33–7.53 (m, 4H), 7.10–7.25 (m, 2H). Example 23 {4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-phenylthio}-acetic acid Ex-23A: To a solution of methyl bromoacetate (1.01 mL, 10.7 mmol) in potassium hydroxide (5M, 20 mL) was added benzenethiol (1.0 mL, 9.7 mmol). The reaction mixture was allowed to stir overnight at ambient temperature. The cloudy solution was then acidified to pH 3. The resulting solid was filtered, washed with water and dried in vacuo to obtain phenylthioacetic acid (0.55 g). The aqueous filtrate was extracted with dichloromethane. The solution of dichloromethane was washed with brine, dried over sodium sulfate and concentrated to obtain additional phenylthioacetic acid (1.49 g). 1 H NMR (CDCl 3 ) δ 743–7.40 (m, 2H), 7.34–7.23 (m, 3H), 3.67 (s, 2H). Ex-23B: To a mixture of alumina chloride (5.5 g, 41.0 mmol) in carbon disulfide (100 mL) was added acetyl chloride (1.17 mL, 16.5 mmol) followed by addition of phenylthioacetic acid (Ex-23A, 1.38 g, 8.2 mmol) and nitromethane (15 mL). The reaction mixture was allowed to stir overnight at ambient temperature and then was poured into ice containing sulfuric acid (6M). The insoluble solid was filtered, washed with, water. After dried in vacuo, the solid was washed with toluene (2×60 mL), filtered and dried under reduced pressure to obtain (4-acetylphenylthio)acetic acid (1.28 g, 74%), m.p. 151–153° C. (Lit. 156–158° C.). 1 H NMR (DMSO-d 6 ) δ 12.80 (bs, 1H), 7.84 (d, J=9 Hz, 2H), 7.36 (d, J=9 Hz, 2H), 3.92 (s, 2H), 2.49 (s, 3H). The title compound was prepared by condensing (4-acetylphenylthio)acetic acid (Ex-23B) and 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde (Ex-3A) in a similar manner as described in Ex-22. Yellow solid, mp 136–138° C. (dec.). 1 H-NMR (DMSO-d 6 ) δ 8.35 (s, 1H), 8.08 (d, J=7.4 Hz, 2H), 8.03 (d, J=16.3 Hz, 1H), 7.93–7.87 (m, 3H), 7.82 (d, J=7.0 Hz, 1H), 7.42 (d, J=7.9 Hz, 2H), 7.37–7.27 (m, 2H), 6.85 (s, 1H), 4.02 (s, 3H), 3.99 (s, 3H), 3.93 (s, 2H). MS m/z=491 ([M+H] + , 100%). Example 24 1-(4-Methylthiophenyl)-3E-(4-thiophen-2-yl-phenyl)-propenone To a mixture of 1-(4-mercapto-phenyl)-3E-(4-thien-2-yl-phenyl)-proenone (Ex-22, 0.33 g, 1.02 mmol) and potassium carbonate (0.54 g, 3.9 mmol) in N,N-dimethylformamide (15 mL) was added iodomethane (0.32 mL, 5.1 mmol). The reaction mixture was allowed to stir at ambient temperature for 2 hours. The insoluble material was filtered. The solution was diluted with ethyl acetate. The solution of ethyl acetate was washed with hydrochloric acid (0.5 M), sodium carbonate (2M) and brine, dried over sodium sulfate, and concentrated. The crude product was purified by flash chromatography. Elution with ethyl acetate (33%, v/v, in hexane) gave the title compound (20 mg, 6%) as a yellow solid, mp 138–140° C. 1 H-NMR (CCDl 3 ) δ 7.98 (d, J=7.8 Hz, 2H), 7.89–7.86 (m, 1H), 7.83 (d, J=15.3 Hz, 1H), 7.76 (s, 3H), 7.53 (d, J=15.1 Hz, 1H), 7.41 (d, J=3.7 Hz, 1H), 7.35–7.31 (m, 3H), 7.13–7.10 (s, 1H), 2.54 (m, 3H). MS m/z=336 (M + , 100%). Example 25 Difluoro-{4-[3E-(4-thiophen-2-yl-phenyl)-acryloyl]-phenylthio}-acetic acid, sodium salt Ex-25A: To a solution of 4-mercaptoacetophenone (prepared according to published procedure, European Patent Application 0271307) (1.16 g, 7.6 mmol) and ethyl bromodifluoroacetate (1.2 mL, 9.15 mmol) in N,N-dimethylformamide (20 mL) was added potassium carbonate (3.2 g, 22.9 mmol). The reaction mixture was allowed to stir overnight at ambient temperature and then was diluted with ethyl acetate. The combined solution of ethyl acetate was subsequently washed with water, hydrochloric acid (0.5M), brine, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography. Elution with ethyl acetate (33%, v/v, in hexane) gave (4-acetyl-phenylthio)-difluoro-acetic acid ethyl ester (1.38 g, 66%). 1 H NMR (CDCl 3 ) δ 7.97 (d, J=8 Hz, 2H), 7.90 (d, J=8 Hz, 2H), 4.29 (q, J=7 Hz, 2H), 2.62 (s, 3H), 1.29 (t, J=7 Hz, 3H). The title compound was prepared by condensing (4-acetyl-phenylthio)-difluoro-acetic acid ethyl ester (Ex-25A) and 4-(thien-2-yl)benzaldehyde (Ex-2A) in a similar manner as described in Ex-22. Yellow solid, 3% yield, mp 118–220° C. 1 H-NMR (CCDl 3 ) δ 8.11 (d, J=7.9 Hz, 2H), 7.95–7.90 (m, 3H), 7.75–7.70 (m, 3H), 7.66 (m, 3H), 7.59 (d, J=5.0 Hz, 1H), 7.16–7.13 (m, 1H). MS m/z=415 ([M−Na] + , 50%), 321 (100%). Example 26 4-[3E-(4-Thiophen-2-yl-phenyl)-acryloyl]-benzenesulfonamide Ex-26A: To a solution of 4-acetyl-benzenesulfonyl chloride (Hoffman, R. V. Org. Syn. VII, 508; 4.18 g, 19.1 mmol) in acetone (30 mL) was added ammonia (28% in water, 8.2 mL, 57.3 mmol) dropwise at 0° C. The reaction mixture was allowed to stir at 0° C. for 30 min. The precipitate was filtered and the residue was washed with water and dried in vacuo to afford 4-acetyl-benzenesulfonamide as a white solid (3.54 g, 93%). 1 H NMR (DMSO-d 6 ) δ 8.10 (d, J=9 Hz, 2H), 8.03 (d, J=9 Hz, 2H), 4.86 (bs, 2H), 2.65 (s, 3H). To a solution of 4-acetyl-benzsulfonamide (Ex-26A, 0.44 g, 2.2 mmol) and 4-thiophen-2-yl-benzaldehyde (Ex-2A, 0.50 g, 2.7 mmol) in DMF (18 mL) was added a solution of NaOH (5 M, 1.77 mL, 8.8 mmol) dropwise. The reaction mixture was allowed to stir at ambient temperature. The reaction was quenched after 2 hours with water. The precipitate was filtered, washed with water, dried in vacuo and purified by stirring in aqueous ethanol overnight. The title compound was collected as a yellow solid (0.45 g, 55%), mp>245° C. 1 H-NMR (DMSO-d 6 ) δ 8.22 (d, J=8.6 Hz, 2H), 7.96–7.89 (m, 6H), 7.77–7.72 (m, 5H), 7.64 (d, J=4.0 Hz, 1H), 7.60 (d, J=4.6, 1H), 7.15 (m, 1H), 6.65 (bs, 1H). MS m/z=369 ([M+H] + , 100%). Example 27 3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-1-(1H-indol-5-yl)-propenone To a solution of 1-(1H-indol-5-yl)-ethanone (Yang, Y., et al., Heterocycles, 1992, 34(6), 1169–1175) (0.26 g, 1.63 mmol) and 3,4-dimethoxy-5-(thien-2-yl)-benzaldehyde (0.45 g, 1.80 mmol, Ex-1D) in ethanol (30 mL) was added a solution of sodium hydroxide (50%, 0.65 mL, 16 mmol). The reaction mixture was allowed to stir overnight at room temperature. The solution was concentrated. The residue was treated with sulfuric acid (1 M), and the cloudy solution was extracted with dichloromethane. The combined dichloromethane extracts were washed with saturated sodium bicarbonate, brine, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography (silica gel, EtOAc/hexane: 1/3 then 1/1) to give 0.17 g (26%) of the title compound as a yellow solid, m.p. 184.5–186° C. MS (direct probe): m/z=389 (M + ). 1 H-NMR (300 MHz, CDCl 3 ) δ 8.43 (s, 1H), 7.99 (d, 1H), 7.12–7.83 (m, 10H), 6.73 (s, 1H), 3.99 (s, 3H), 3.88 (s, 3H). Example 28 3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-1-(1-methyl-1H-indol-5-yl)-propenone Ex-28A: To a solution of 1-(1H-indol-5-yl)-ethanone (Yang, Y. et al, Heterocycles, 1992, 34(6), 1169–1175; 0.45 g, 2.8 mmol) were added iodomethane (3 mL) and cesium carbonate (2.3 g, 7.1 mmol). The reaction mixture was allowed to stir at 55° C. for 1.5 day during which additional iodomethane (11 mL) was added. The reaction was quenched with water. The aqueous solution was extracted with ether. The solution of ether was washed with saturated solution sodium bicarbonate, brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography. Elution with ethyl acetate (33%, v/v, in hexane) gave 1-(1-methyl-1H-indol-5-yl)-ethanone (0.25 g, 51%). 1 H NMR (CDCl 3 ) δ 8.30 (s, 1H), 7.91 (dd, J=1.2, 8.1 Hz, 1H), 7.34 (d, J=8.6 Hz, 1H), 7.12 (d, J=3.2 Hz, 1H), 6.61 (d, J=3.0, 1H), 3.82 (s, 3H), 2.66 (s, 3H). The title compound was prepared by condensing 1-(1-methyl-1H-indol-5-yl)-ethanone (Ex-28A) and 3,4-dimethoxy-5-(thien-2-yl)benzaldehyde (Ex-1D) in a similar manner as described in Ex-27. Yellow solid, 43% yield, mp 70–71° C. 1 H-NMR (CDCl 3 ) δ 8.41 (s, 1H), 8.00 (dd, J=1 Hz, 7 Hz, 1H), 7.80 (d, J=15 Hz, 1H), 7.63 (d, J=15.0 Hz, 1H), 7.58–7.55 (m, 2H), 7.43–7.40 (m, 2H), 7.15–7.12 (m, 3H), 6.66 (d, J=3 Hz, 1H), 3.99 (s, 3H), 3.88 (s, 3H), 3.86 (s, 3H). Anal. (C 24 H 21 NOS.0.25H 2 O) Calc. C, 70.65; H, 5.31; N, 3.43; S, 7.86; found C, 70.64; H, 5.35; N, 3.43; S, 7.90. Example 29 4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid Ex-29A: 2-Hydroxy-4-methoxybenzaldehyde (6.0 g, 39 mmol) was dissolved in dichloromethane (50 mL) and cooled to 0° C. using an ice-water bath. Bromine (6.8 g, 43 mmol) in dichloromethane (2 mL) was added dropwise to the cooled solution and stirred for 2 h at 0° C. The mixture was warmed to room temperature and stirred for an additional 1 h and the resulting yellow precipitate was collected. Recrystallization (ethyl acetate/hexanes) yielded 7.1 g (80%) of 5-bromo-2-hydroxy-4-methoxybenzaldehyde as white needles, m.p. 63–64° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 11.43 (s, 1H), 9.69 (s, 1H), 7.68 (s, 1H), 6.48 (s, 1H), 3.95 (s, 3H). Anal. Calcd. for C 8 H 7 BrO 3 : C, 41.59; H, 3.05. Found: C, 41.86; H, 3.05. Ex-29B: 5-Bromo-2-hydroxy-4-methoxybenzaldehyde obtained from Ex-29A (1.5 g, 6.5 mmol) and thiophene-2-boronic acid (0.91 g, 7.1 mmol) were dissolved in tetrahydrofuran (15 mL). Nitrogen was bubbled into the solution for 10 min followed by the sequential addition of potassium fluoride (0.80 g, 14 mmol, spray-dried) and bis(tri-t-butylphosphine)palladium(0) (0.033 g, 0.065 mmol). The solution was immediately heated to 60° C. and aged for 1.5 h. Upon completions, as determined by HPLC, the reaction was diluted with water (25 mL) and extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over sodium sulfate and concentrated to a brown solid. Silica gel chromatography (ethyl acetate/hexanes, 1:3) gave 1.46 g (97%) of 2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde as a yellow solid, m.p. 118–119° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 11.48 (s, 1H), 9.79 (s, 1H), 7.72 (s, 1H), 7.37 (dd, 1H), 7.31 (dd, 1H), 7.08 (dd, 1H), 6.54 (s, 1H), 3.98 (s, 3H). Anal. Calcd. for C 8 H 7 O 3 S: C, 61.52; H, 4.30; S, 13.69. Found: C, 61.12; H, 4.34; S, 13.56. Ex-29C: To a solution of 2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde from Ex-29B (0.10 g, 0.43 mmol) in N,N-dimethylformamide (3 mL) was added potassium carbonate (0.18 g, 1.3 mmol) and the resulting yellow slurry was heated to 80° C. Once at 80° C., 1-bromo-2-(2-methoxyethoxy)ethane (0.24 g, 1.3 mmol) was added dropwise in three equal portions with stirring at 1 h intervals. After the last addition, the reaction was stirred for an additional 1 h at 80° C. and cooled to room temperature. The mixture was diluted with water (15 mL) and extracted with ethyl acetate (3×15 mL). The combined organic layers was sequentially washed with a saturated ammonium chloride solution (1×15 mL), water (1×15 mL), and brine (1×15 mL), dried over sodium sulfate, and concentrated to a brown oil. Silica gel chromatography (ethyl acetate/hexanes, 4:1) afforded 0.13 g (87%) of 4-methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-benzaldehyde as a pale yellow oil. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.38 (s, 1H), 8.12 (s, 1H), 7.44 (dd, 1H), 7.30 (dd, 1H), 7.07 (dd, 1H), 6.57 (s, 1H), 4.33 (t, 2H), 4.00 (s, 3H), 3.94 (t, 2H), 3.74 m, 2H), 3.59 (m, 2H), 3.40 (s, 3H). HRMS (EI) Calcd. for C 17 H 20 O 5 S: 336.1031. Found: 336.1027. 4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-benzaldehyde obtained from Ex-29C (0.13 g, 0.37 mmol) and 4-acetylbenzoic acid (0.061 g, 0.37 mmol) were dissolved in a tetrahydrofuran-methanol solution (2 mL, 7:3). After complete dissolution, lithium methoxide (0.057 g, 1.5 mmol) was added and the resulting bright orange slurry was stirred in the dark at room temperature for 4 h. Upon completion, as determined by HPLC, the mixture was diluted with water (10 mL), acidified with a 1 N hydrochloric acid solution, and extracted with ethyl acetate (3×15 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was taken up in ethyl alcohol (3 mL) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. The resulting precipitate was collected and dried in vacuo to yield 0.14 g (85%) of the title compound as a yellow solid, m.p. 145–146° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.22 (m, 3H), 8.09 (d, 2H), 8.01 (d, 2H), 7.66 (dd, 1H), 7.52 (d, 1H), 7.13 (dd, 1H), 6.88 (s, 1H), 4.36 (t, 2H), 4.00 (s, 3H), 3.88 (t, 2H), 3.65 (m, 2H), 3.46 (m, 2H), 3.22 (s, 3H). Anal. Calcd. for C 26 H 26 NO 7 S: C, 64.71; H, 5.43; S, 6.64. Found: C, 64.64; H, 5.44; S, 6.61. Example 30 4-[3E-(2-Fluoro-4-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-30A: 2-Fluoro-4-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-3A from thiophene-2-boronic acid and 4-bromo-2-fluorobenzaldehide (93% yield). 1 H-NMR (300 MHz, d 6 -DMSO): 10.13 (s, 1H), 7.81 (d, 1H, J=8.0 Hz), 7.76 (m, 1H), 7.67 (m, 2H), 7.59 (dd, 1H J=8.0 and 2.1 Hz), 7.17 (dd, 1H J=5.2 and 3.7 Hz). The title compound was prepared by condensing 2-fluoro-4-thiophen-2-yl-benzaldehyde (Ex-30A) and 4-acetylbezoic acid in a similar manner as described in Ex-3. Yellow solid, 71% yield, m.p.>260° C. 1 H-NMR (300 MHz, d 6 -DMSO): 8.19 (d, 2H, J=8.4 Hz), 8.12 (d, 1H, J=8 Hz), 8.06 (d, 2H, J=8 Hz), 7.95 (d, 1H, J=16 Hz), 7.80 (d, 1H, J=16 Hz), 7.71 (d, 1H, J=3.5 Hz), 7.62 (m, 2H), 7.56 (d, 1H, J=8 Hz), 7.15 (m, 1H). MS m/z=352 ([M] + , 100%). HRMS (EI) Calcd. for C 20 H 13 NO 3 S: 352.0569. Found: 352.0560. Example 31 4-[3E-(2,4-Dimethoxy-5-pyrimidin-5-yl-phenyl)-acryloyl]-benzoic acid Ex-31A: 2,4-Dimethoxy-5-pyrimidin-5-yl-benzaldehyde was prepared from 5-bromo-2,4-dimethoxybenzaldehyde and pyrimidine-5-boronic acid in a similar manner as described in Ex-3A, 98% yield. 1 H-NMR (CDCl 3 ) δ 10.37 (s, 1H), 9.15 (s, 1H), 8.87 (s, 2H) 7.86 (s, 1H), 6.57 (s, 1H), 4.03 (s, 3H), 3.96 (s, 3H). The title compound was prepared by condensing 2,4-dimethoxy-5-pyrimidin-5-yl-benzaldehyde (Ex-31A) and 4-acetylbezoic acid in a similar manner as described in Ex-3. Yellow solid, mp>260° C., 26% yield. 1 H-NMR (DMSO-d 6 ) δ 9.11 (s, 1H), 8.96 (s, 2H), 8.13–8.16 (m, 3H), 8.01–8.09 (m, 3H), 7.90 (d, J=15 Hz, 1H), 6.85 (s, 1H), 3.99 (s, 3H), MS m/z=391 ([M+H] + , 100%). HRMS (ES+) Calcd. for C 22 H 18 N 2 O 5 : 391.1294. Found: 391.1295. Example 32 4-[3E-(2-Cyclopropylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-32A: 2-Cyclopropylmethoxy-4-methoxy-5-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-29C from 2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex. 29B) and chloromethyl-cyclopropane, 18% yield. 1 H-NMR (CDCl 3 ) δ 10.41 (s, 1H), 8.24 (s, 1H), 7.43 (d, 1H), 7.29 (d, 1H), 7.06 (t, 1H), 6.45 (s, 1H), 3.95 (m, 5H), 1.31 (m, 1H), 0.68 (m, 2H), 0.40 (q, 2H). The title compound was prepared by condensing 2-cyclopropylmethoxy-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-32B) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 187–191° C. 1 H-NMR (DMSO-d6) δ 8.22 (d, 2H), 8.19 (s, 1H), 7.01 (m, 4H), 7.62 (d, 1H), 7.47 (d, 1H), 7.09 (t, 1H), 6.76 (s, 1H), 4.06 (d, 2H), 3.94 (s, 3H), 1.34 (m, 1H), 0.62 (q, 2H), 0.38 (q, 2H). MS m/z=434 ([M] + , 82%), 363 (100%). 10%. Anal. for C 25 H 22 O 5 S. HRMS m/z: calc. 435.1266, found 435.1266. Example 33 4-{3E-[5-(3,5-Dimethyl-isoxazol-4-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid Ex-33A: 5-(3,5-Dimethyl-isoxazol-4-yl)-2,4-dimethoxy-benzaldehyde was prepared from 5-bromo-2,4-dimethoxybenzaldehyde and 3,5-dimethyl-isoxazole-4-boronic acid in a similar manner as described in Ex-3A, 75% yield. 1 H-NMR (CDCl 3 ) δ 10.34 (s, 1H), 7.63 (s, 1H), 6.52 (s, 1H), 4.00 (s, 3H), 3.90 (s, 3H), 2.12 (s, 6H). The title compound was prepared by condensing 5-(3,5-dimethyl-isoxazol-4-yl)-2,4-dimethoxy-benzaldehyde (Ex-33A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp>260° C., 7% yield. 1 H-NMR (DMSO-d 6 ) δ 8.15 (d, J=8 Hz, 2H), 8.04 (d, J=16 Hz, 1H), 8.02 (d, J=8 Hz, 2H), 7.89 (s, 1H), 7.81 (d, J=16 Hz, 1H), 6.79 (s, 1H), 4.00 (s, 3H), 3.97 (s, 3H), 2.23 (s, 3H) 2.05 (s, 3H) MS m/z=407 ([M] + , 60%), 376 (100%). HMRS (EI) calcd. for C 23 H 21 NO 6 : 407.1369; found: 407.1375. Example 34 4-[3E-(4-Methoxy-2-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-34A: A solution of 2-hydroxy-4-methoxy-benzaldehyde (5.0 g, 32.86 mmol) in dichloromethane (65 mL) was cooled to 0° C. and then pyridine (13.3 mL, 164.4 mmol) was added in 1 portion. Triflic anhydride (14.8 mL, 87.97 mmol) was then added over 2 h while maintaining an internal temperature below 5° C. The resulting solution was allowed to warm to room temperature overnight and then was slowly poured into ice water (100 mL). After diluting further with 1 N HCl (100 mL) the solution was extracted with dichloromethane (2×100 mL). The organic phase was washed with sat NaHCO 3 (100 mL) and dried over magnesium sulfate. The solvent was then removed under reduced pressure. Silica gel chromatography (hexane/ethyl acetate, 1:1) gave 1.65 g (18%) of the desired trifluoro-methanesulfonic acid 2-formyl-5-methoxy-phenyl ester. 1 H-NMR (300 MHz, CDCl 3 ): 10.12 (s, 1H), 7.94 (dd, 1H, J=8.7 Hz), 7.03 (dd, 1H, J=8.7 and 2.4 Hz), 6.87 (d, 1H, J=2.4 Hz), 3.92 (s, 3H). Ex-34B: A solution of trifluoro-methanesulfonic acid 2-formyl-5-methoxy-phenyl ester (Ex-34A, 1.6 g, 5.63 mmol) in 1,4-dioxane (15 mL) was stirred at room temperature under nitrogen for 5 min. Thiophene-2-boronic acid (1.08 g, 8.44 mmol), tetrakis(triphenylphosphine)palladium(0) (0.65 g, 0.56 mmol) and a potassium phosphate (2.2 g, 10.36 mmol) were then added and the resulting mixture was heated to 95° C. under nitrogen overnight. Upon cooling to room temperature the reaction was diluted with EtOAc (25 mL) and water (25 mL) and the layers were cut. The organic phase was concentrated under reduced pressure. Silica gel chromatography (hexane/ethyl acetate, 4:1) gave 1.1 g (90%) of the desired 4-methoxy-2-thiophen-2-yl-benzaldehyde product. 1 H-NMR (300 MHz, CDCl 3 ): 10.06 (s, 1H), 8.03 (m, 1H), 7.45 (m, 1H), 7.14 (m, 1H), 7.09 (m, 1H), 7.00 (m, 2H), 3.91 (s, 3H). The title compound was prepared by condensing 4-methoxy-2-thiophen-2-yl-benzaldehyde (Ex-34A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 61% yield, m.p. 209–211° C. 1 H-NMR (300 MHz, d 6 -DMSO): 8.14 (m, 3H), 8.04 (d, 2H, J=9.2 Hz), 7.89 (d, 1H, J=15.5 Hz), 7.76 (d, 1H, J=15.5 Hz), 7.70 (d, 1H, J=5.0 Hz), 7.18 (dd, 1H, J=5.6 and 3.6 Hz), 7.11 (d, 1H, J=2.1 Hz), 7.05 (dd, 1H, J=8.8 and 1.8 Hz), 6.98 (d, 1H, J=1.8 Hz), 3.83 (s, 3H). MS m/z=364 ([M] + , 100%). HRMS (EI) Calcd. for C 21 H 16 O 4 S: 364.0769. Found: 364.0761. Example 35 2-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid The title compound was prepared by condensing 2,4-dimethoxy-5-(thiophen-2-yl)-benzaldehyde (Ex-6A) and 2-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 47% yield, mp 196–198° C. 1 H-NMR (DMSO-d6) δ 8.00 (s, 1H), 7.84 (d, 1H), 7.61 (m, 3H), 7.45 (m, 3H), 7.21 (d, 1H), 7.08 (t, 1H), 6.75 (s, 1H), 3.95 (s, 3H), 3.86 (s, 3H). MS m/z=394 ([M]+, 100%). Anal. calculated for C22H18O5S: C, 66.99; H, 4.60; S, 8.13. found C, 67.08; H, 4.17; S, 7.97. Example 36 2-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-indole-1-carboxylic acid tert-butyl ester Ex-36A: 2-(5-Formyl-2,4-dimethoxy-phenyl)-indole-1-carboxylic acid tert-butyl ester was prepared from 5-bromo-2,4-dimethoxybenzaldehyde and N-Boc-indole-2-boronic acid in a similar manner as described in Ex-3A. Yellow oil, 79% yield. 1 H-NMR (CDCl3) δ 10.36 (s, 1H), 8.15 (d, J=8 Hz, 1H), 7.88 (s, 1H), 7.45 (d, J=8 Hz, 3H), 7.27–7.35 (m, 1H), 7.19–7.27 (m, 1H), 6.52 (s, 1H), 6.47 (s, 1H), 4.00 (s, 3H), 3.86 (s, 3H), 1.42 (s, 9H). The title compound was prepared by condensing 2-(5-formyl-2,4-dimethoxy-phenyl)-indole-1-carboxylic acid tert-butyl ester (Ex-36A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 8% yield, mp 182–183° C. 1 H-NMR (CDCl 3 ) δ 8.21 (d, J=8 Hz, 2H), 8.19 (d, J=13 Hz, 1H), 8.16 (d, J=7 Hz, 1H), 8.07 (d, J=8 Hz, 2H), 7.69 (s, 1H), 7.54 (d, J=7 Hz, 1H), 7.52 (d, J=13 Hz, 1H), 7.29–7.35 (m, 1H), 7.23 (d, J=7 Hz, 1H), 6.55 (s, 1H), 6.50 (s, 1H), 4.00 (s, 3H), 3.85 (s, 3H), 3.81 (s, 3H). MS m/z=528 ([M+H] + , 100%). Anal. calc. for C 31 H 29 NO 7 H 2 O: C, 68.25; H, 5.73; N, 2.56; found: C, 68.63; H, 5.62; N, 2.45. Example 37 4-[3E-(2,6-Dimethoxy-4-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-37A: 2,6-Dimethoxy-4-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-34A and Ex-34B. 75% yield, m.p. 168–170° C. 1 H-NMR (300 MHz, CDCl 3 ): 10.48 (s, 1H), 7.43 (dd, 1H, J=3.6 and 1.3 Hz), 7.41 (d, 1H, J=5.3 Hz), 7.13 (dd, 1H, J=5.3 and 3.6 Hz), 6.79 (s, 2H), 3.96 (s, 6H). The title compound was prepared by condensing 2,6-dimethoxy-4-thiophen-2-yl-benzaldehyde (Ex-37A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 79% yield, m.p. 256–258° C. 1 H-NMR (300 MHz, d 6 -DMSO): 8.11 (d, 1H, J=15.9 Hz), 8.10 (m, 4H), 8.05 (d, 1H, J=15.9 Hz), 7.73 (d, 1H, J=3.6 Hz), 7.61 (d, 1H, J=5.3 Hz), 7.16 (dd, 1H, J=5.3 and 3.6 Hz), 6.95 (s, 2H), 3.98 (s, 6H). MS m/z=394 ([M] + , 100%). HRMS (EI) Calcd. for C 22 H 18 O 5 S: 394.0875. Found: 394.0877. Example 38 4-{3E-[5-(2,4-Dimethoxy-pyrimidin-5-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid Ex-38A: 5-(2,4-Dimethoxy-pyrimidin-5-yl)-2,4-dimethoxy-benzaldehyde was prepared from 5-bromo-2,4-dimethoxybenzaldehyde and 2,4-Dimethoxy-pyrimidin-5-boronic acid in a similar manner as described in Ex-3A, 75% yield. 1 H-NMR (CDCl 3 ) δ 10.34 (s, 1H), 8.13 (s, 1H), 7.74 (s, 1H), 6.51 (s, 1H), 4.03 (s, 3H), 3.99 (s, 3H), 3.95 (s, 3H), 3.88 (s, 3H). The title compound was prepared by condensing 5-(2,4-dimethoxy-pyrimidin-5-yl)-2,4-dimethoxy-benzaldehyde (Ex-38A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 203–205° C., 22% yield. 1 H-NMR (DMSO-d 6 ) δ 8.11–9.15 (m, 3H), 7.99–8.06 (m, 3H), 7.88 (s, 1H), 7.76 (d, J=17 Hz, 1H), 6.76 (s, 1H), 3.96 (s, 3H), 3.90 (s, 3H), 3.83 (s, 3H) 3.81 (s, 3H). MS m/z=451 ([M+H] + ). HRMS (ES+) Calcd. for C 24 H 22 N 2 O 7 : 451.1505. Found: 451.1524. Example 39 4-[3E-(2,4-Dimethoxy-6-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-39A: 2,4-Dimethoxy-6-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-34A, 40% yield. 1 H-NMR (CDCl 3 ) δ 10.02 (s, 1H), 7.40 (d, 1H), 7.07 (m, 2H), 6.58 (d, 1H), 6.50 (d, 1H), 3.93 (s, 3H), 3.89 (s, 3H). The title compound was prepared by condensing 2,4-dimethoxy-6-thiophen-2-yl-benzaldehyde (Ex-39A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 61% yield, mp 231° C. (dec.). 1 H-NMR (DMSO-d6) δ 8.02 (d, 2H), 7.93 (d, 2H), 7.73 (m, 3H), 7.15 (t, 1H), 7.07 (d, 1H), 6.72 (d, 1H), 6.62 (d, 1H). MS m/z=394 ([M] + , 6%), 245 (100%). HRMS m/z: calc. 395.0953, found 395.0949. Example 40 4-{3E-[2,4-Dimethoxy-5-(5-methyl-thiophen-2-yl)-phenyl]-acryloyl}-benzoic acid Ex-40A: 2,4-Dimethoxy-5-(5-methyl-thiophen-2-yl)-benzaldehyde was prepared from 5-bromo-2,4-dimethoxybenzaldehyde and 5-methyl-thiophene-2-boronic acid in a similar manner as described in Ex-3A, 100% yield. 1 H-NMR (CDCl 3 ) δ 10.33 (s, 1H), 8.05 (s, 1H), 7.22 (d, J=4 Hz, 1H), 6.72 (d, J=4 Hz, 1H), 6.49 (s, 1H), 4.00 (s, 3H), 3.97 (s, 3H), 2.50 (s, 3H). HMRS (EI) calcd. for C 14 H 14 O 3 S: 262.0664; found: 262.0665. The title compound N was prepared by condensing 2,4-dimethoxy-5-(5-methyl-thiophen-2-yl)-benzaldehyde (Ex-40A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 213–215° C., 27% yield. 1 H-NMR (DMSO-d 6 ) δ 8.18 (d, J=7 Hz, 2H), 8.17 (s, 1H), 8.00–8.06 (m, 3H), 7.85 (d, J=15 Hz, 1H), 7.42 (d, J=4 Hz, 1H), 6.78 (m, 2H), 3.96 (s, 3H), 3.95 (s, 3H), 2.42 (s, 3H). MS m/z=408 ([M] + , 100%). HMRS (EI) calcd. for C 23 H 20 O 5 S: 408.1031; found: 408.1023. Example 41 4-[3E-(4-Methoxy-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-41A: 4-Methoxy-3-(thiophen-2-yl)-benzaldehyde was prepared from 3-bromo-4-methoxybenzaldehyde and thiophene-2-boronic acid in a similar manner as described in Ex-3A. Orange oil, 96% yield. 1 H-NMR (CDCl 3 ) δ 9.94 (s, 1H), 8.16 (d, J=1.8 Hz, 1H), 7.80 (dd, J=2.4, 8.4 Hz, 1H), 7.57 (dd, J=1.8, 3.6 Hz, 1H), 7.38 (d, J=5.1 Hz, 1H), 7.12 (dd, J=3.6, 5.1 Hz, 1H), 7.09 (d, J=8.4 Hz, 1H), 4.02 (s, 3H). HRMS m/z: calc. 218.0402, found 218.0406. The title compound was prepared by condensing 4-methoxy-3-(thiophen-2-yl)-benzaldehyde (Ex-41A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 219–220° C., 71% yield. 1 H-NMR (DMSO-D 6 ) δ 13.36 (br s, 1H), 8.25–8.31 (m, 3H), 8.11 (d, J=8 Hz, 2H), 7.85–7.98 (m, 3H), 7.78–7.80 (m, 1H), 7.61 (d, J=5 Hz, 1H), 7.25 (d, J=9 Hz, 1H), 7.17 (dd, J=4, 6 Hz, 1H), 3.99 (s, 3H). HRMS m/z=calc. 365.0848, found 365.0833. Example 42 4-[3E-(3-Thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-42A: 3-(Thiophen-2-yl)-benzaldehyde was prepared from 3-bromobenzaldehyde and thiophene-2-boronic acid in a similar manner as described in Ex-3A. Orange oil, 93% yield. 1 H-NMR (CDCl 3 ) δ 10.06 (s, 1H), 8.10 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.78 (d, J=7.2 Hz, 1H), 7.55 (dd, J=7.2, 8.4 Hz, 1H), 7.40 (dd, J=1.5, 3.6 Hz, 1H), 7.34 (dd, J=1.5, 5.3 Hz, 1H), 7.11 (dd, J=3.6, 5.3 Hz, 1H). HRMS m/z: calc. 188.0296. found 188.0293. The title compound was prepared by condensing 3-(thiophen-2-yl)-benzaldehyde (Ex-42A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 238° C. (dec), 71% yield. 1 H-NMR (DMSO-D 6 ) δ 13.40 (bs, 1H), 8.29 (d, J=8 Hz, 2H), 8.22 (s, 1H), 8.13 (d, J=8 Hz, 2H), 8.04 (s, 1H), 7.87 (s, 1H), 7.83 (d, J=8 Hz, 1H), 7.73 (d, J=9 Hz, 1H), 7.69 (d, J=4 Hz, 1H), 7.63 (d, J=5 Hz, 1H), 7.52 (t, J=8 Hz, 1H), 7,20 (dd, J=4, 5 Hz, 1H). HRMS m/z=calc. 335.0742, found 335.0749. Example 43 3-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid The title compound was prepared by condensing 2,4-dimethoxy-5-(thiophen-2-yl)-benzaldehyde (Ex-6A) and 3-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 65% yield, mp 179–182° C. 1 H-NMR (DMSO-d6) δ 8.54 (s, 1H), 8.39 (d, 1H), 8.25 (s, 1H), 8.15 (d, 1H), 8.04 (d, 1H), 7.90 (d, 1H), 7.67 (m, 2H), 7.48 (d, 1H), 7.09 (t, 1H), 6.81 (s, 1H), 3.98 (s, 3H), 3.97 (s, 3H). MS m/z=394 ([M] + , 72%), 363 (100%). Anal. calculated for C22H18O5S: C, 66.99; H, 4.60; S, 8.13; found C, 66.80; H, 4.60; S, 8.07. Example 44 4-[3E-(3-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid Ex-44A: 3-Benzo[b]thiophen-2-yl-2-hydroxy-4-methoxy-benzaldehyde was prepared through Suzuki coupling as described in Ex-3A using 3-bromo-2-hydroxy-4-methoxybenzaldehyde (obtained as a minor product from Ex-29A). 1 H-NMR (CDCl 3 ) δ 12.08 (s, 1H), 9.80 (s, 1H), 7.80–7.87 (m, 2H), 7.70 (s, 1H), 7.56 (d, J=9 Hz, 1H), 7.31–7.35 (m, 2H), 6.71 (d, J=9 Hz, 1H), 3.97 (s, 3H). HRMS m/z: calc. 284.0507, found 284.0502. Ex-44B: 3-Benzo[b]thiophen-2-yl-2-hydroxy-4-methoxy-benzaldehyde (Ex-44A, 57.4 mg, 0.202 mmol) was dissolved in acetone (5 mL) and potassium carbonate (31 mg, 0.22 mmol) was added. Methyl iodide (25 uL, 0.40 mmol) was added and the solution was heated to reflux for 3.5 h. After cooling, the crude reaction mix was concentrated on the rotavap. The resulting residue was taken up in 10 mL of a 1:9 mix of saturated, aqueous NH 4 Cl to water and extracted with EtOAc (2×15 mL). The organic phase was dried over sodium sulfate, filtered, and concentrated to provide 58.5 mg of 3-benzo[b]thiophen-2-yl-2,4-dimethoxy-benzaldehyde as an orange, oily residue which was used without further purification, 97% yield. 1 H-NMR (CDCl 3 ) δ 10.31 (s, 1H), 7.92 (d, J=9 Hz, 1H), 7.81–7.88 (m, 2H), 7.56 (d, 1H), 7.33–7.39 (m, 2H), 6.88 (d, J=9 Hz, 1H), 3.91 (s, 3H), 3.64 (s, 3H). The title compound was prepared by condensing 3-benzo[b]thiophen-2-yl-2,4-dimethoxy-benzaldehyde (Ex-44B) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 237° C. (dec.), 64% yield. 1 H-NMR (DMSO-d 6 ) δ 13.37 (bs, 1H), 8.20–8.25 (m, 3H), 8.11 (d, J=8 Hz, 2H), 8.02 (d, J=8 Hz, 1H), 7.96 (d, J=9 Hz, 2H), 7.88–7.91 (m, 1H), 7.65 (s, 1H), 7.35–7.43 (m, 2H), 7.14 (d, J=9 Hz, 1H), 3.90 (s, 3H), 3.53 (s, 3H). HRMS m/z=calc. 445.1110, found 445.1112. Example 45 4-[3E-(2-Methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-45A: 2-Methoxy-5-(thiophen-2-yl)-benzaldehyde was prepared from 5-bromo-2-methoxybenzaldehyde and thiophene-2-boronic acid in a similar manner as described in Ex-3A. 1 H NMR (CDCl 3 ) δ 10.49 (s, 1H), 8.07 (d, J=3 Hz, 1H), 7.79 (dd, J=3, 9.0 Hz, 1H), 7.28–7.26 (m, 2H), 7.09–7.06 (m, 1H), 7.02 (d, J=9 Hz, 1H), 3.97 (s, 3H). The title compound was prepared by condensing 2-methoxy-5-(thiophen-2-yl)-benzaldehyde (Ex-45A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 195–196° C. 1 H-NMR (DMSO-d 6 ) δ 8.23–8.20 (m, 3H), 8.08–7.96 (m, 4H), 7.67 (dd, J=2.1, 6.8 Hz, 1H), 7.55 (d, J=3.8 Hz, 1H), 7.49 (d, J=5.1 Hz, 1H), 7.16–7.11 (m, 2H), 3.90 (s, 3H). MS m/z=364 (M + , 100%). Example 46 4-[3E-(2,4-Dimethoxy-5-pyrazin-2-yl-phenyl)-acryloyl]-benzoic acid Ex-46A: 5-Bromo-2,4-dimethoxybenzaldehyde (4.92 g, 20.1 mmol) was dissolved in benzene (41 mL). Ethylene glycol (3 mL, 54 mmol) and p-toluenesulfonic acid (25 mg, 0.13 mmol) were added and the solution was refluxed with a Dean-Stark trap attached. After 6 h, the reaction was cooled and washed with water (1×20 mL), saturated, aqueous NaHCO 3 (1×20 mL), and water (1×20 mL). The organic phase was dried over sodium sulfate, filtered, concentrated, and dried to provide 5.32 g of 2-(5-bromo-2,4-dimethoxy-phenyl)-[1,3]dioxolane as a faint yellow oil which solidified upon standing (92% yield). 1 H-NMR (CDCl 3 ) δ 7.67 (s, 1H), 6.47 (s, 1H), 6.06 (s, 1H), 4.11–4.13 (m, 2H), 3.98–4.03 (m, 2H), 3.91 (s, 3H), 3.87 (s, 3H). HRMS (ES+) Calcd. for C 11 H 13 BrO 4 : 289.0075. Found: 289.0077. Ex-46B: 2-(5-Bromo-2,4-dimethoxy-phenyl)-[1,3]dioxolane (Ex-46A, 4.78 g, 10.5 mmol) was dissolved in dioxane (75 mL) and the solution was purged with nitrogen for 15 min. Pd(OAc) 2 (188 mg, 0.84 mmol), Et 3 N (6.91 mL, 49.6 mmol), and 2-(dicyclohexylphosphino)biphenyl (1.16 g, 3.31 mmol) were added. 4,4,5,5-Tetramethyl-[1,3,2]dioxaborolane (3.6 mL, 24.8 mmol) was added slowly, accompanied by gas evolution and the darkening of the reaction solution. The solution was heated at reflux for 2.5 h and then cooled. Saturated, aqueous NH 4 Cl (60 mL) and water (20 mL) were added and the solution extracted with EtOAc (1×100 mL). The organic phase was dried over sodium sulfate, filtered, and concentrated to a dark oil. The oil was purified via silica gel chromatography (1:1 EtOAc/hexanes after a column pre-wash of 5% Et 3 N in 1:1 EtOAc/hexanes) to provide 3.27 g of 2-(5-[1,3]dioxolan-2-yl-2,4-dimethoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane as a yellow solid (with some starting borolane present), 59% yield. 1 H-NMR (CDCl 3 ) δ 7.85 (s, 1H), 6.39 (s, 1H), 6.07 (s, 1H), 4.13–4.18 (m, 2H), 3.98–4.02 (m, 2H), 3.89 (s, 3H), 3.84 (s, 3H), 1.33 (s, 9H). Ex-46C: 2-(5-[1.3]Dioxolan-2-yl-2,4-dimethoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Ex-46B, 2.22 g, 6.60 mmol, containing borolane impurity) was dissolved in DME (60 mL) and 2-iodopyrazine (0.59 mL, 6.0 mmol) was added. 2M aqueous Na 2 CO 3 (17.8 mL, 35.6 mmol) was added and the mixture was purged with nitrogen for 20 min. Tetrakis(triphenylphosphine)palladium(0) (0.69 g, 0.60 mmol) was added and the mixture was heated at reflux for 2.5 h. After cooling, water (50 mL) was added and the mixture was extracted with CH 2 Cl 2 (2×30 mL). The organic phase was washed with brine (1×20 mL), dried over sodium sulfate, filtered, and concentrated. Purification of the resulting yellow-orange solids via silica chromatography (50–80% EtOAc/hexanes) provided 1.02 g of 2-(5-[1,3]dioxolan-2-yl-2,4-dimethoxy-phenyl)-pyrazine as a yellow solid (59% yield). 1 H-NMR (CDCl 3 ) δ 9.10 (d, J=2 Hz, 1H), 8.61 (m, 1H), 8.39 (d, J=3 Hz, 1H), 8.07 (s, 1H), 6.57 (s, 1H), 6.14 (s, 1H), 4.13–4.18 (m, 2H), 4.01–4.05 (m, 2H), 3.95 (s, 3H), 3.93 (s, 3H). Ex-46D: 2-(5-[1,3]Dioxolan-2-yl-2,4-dimethoxy-phenyl)-pyrazine (1.02 g, 3.54 mmol) was dissolved in acetone and p-toluenesulfonic acid (100 mg, 0.53 mmol) and water (5 mL) were added. The solution was stirred for 3 h at room temperature, then concentrated on the rotavap. The resulting mixture was diluted with water (50 mL) and extracted with EtOAc (3×100 mL). The organic phase was washed with 25% saturated aqueous NaHCO 3 , dried over sodium sulfate, filtered, and concentrated. Drying gave 0.30 g of 2,4-dimethoxy-5-pyrazin-2-yl-benzaldehyde as a yellow solid (18% yield). 1 H-NMR (CDCl 3 ) δ 10.35 (s, 1H), 9.06 (d, J=2 Hz, 1H), 8.63–8.65 (m, 1H), 8.45 (d, J=2 Hz, 1H), 8.39 (s, 1H), 6.56 (s, 1H), 4.03 (s, 3H), 4.01 (s, 3H). HRMS m/z: calc. 244.0848, found 244.0853. The title compound was prepared by condensing 2,4-dimethoxy-5-pyrazin-2-yl-benzaldehyde (Ex-46D) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 238° C. (dec.), 4% yield. 1 H-NMR (DMSO-D 6 ) δ 9.04 (d, J=2 Hz, 1H), 8.75–8.76 (m, 1H), 8.56 (d, J=2 Hz, 1H), 8.32 (s, 1H), 8.19 (d, J=9 Hz, 2H), 8.05–8.11 (m, 3H), 7.83 (d, J=16 Hz, 1H), 6.90 (s, 1H), 4.05 (s, 3H), 4.00 (s, 3H). HRMS m/z=calc. 391.1294. found 391.1313. Example 47 4-{3E-[4-(1-Carboxy-1-methyl-ethoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid Ex-47A: 5-Bromo-4-hydroxy-2-methoxy-benzaldehyde was prepared in an analogous fashion as described in Ex-29A using 4-hydroxy-2-methoxybenzaldehyde. The crude solid was slurried in water to remove residual HBr and dried in vacuo to give the bromide as an off-white solid (98%), mp 199–201° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 11.58 (s, 1H), 10.07 (s, 1H), 7.75 (s, 1H), 6.69 (s, 1H), 3.87 (s, 3H). MS (EI) m/z=230 ([M] + , 100%). Anal. Calcd. for C 8 H 7 BrO 3 .¼H 2 O: C, 40.79; H, 3.21; Found: C, 40.66; H, 3.01. Ex-47B: 4-Hydroxy-2-methoxy-5-thiophen-2-yl-benzaldehyde was prepared in an analogous fashion as described in Ex-29B. Silica gel chromatography (ethyl acetate/hexanes, 2:1) gave the expected product as a solid (85%), mp 200° C. (dec.). 1 H-NMR (300 MHz, CDCl 3 ) δ 10.31 (s, 1H), 7.89 (s, 1H), 7.42 (dd, 1H, J=4.8, 1.2 Hz), 7.14–7.19 (m, 2H), 6.59 (s, 1H), 6.14 (brs, 1H), 3.94 (s, 3H). MS (EI) m/z: 234 ([M] + , 100%). Anal. Calcd. for C 12 H 10 O 3 S.H 2 O: C, 57.13; H, 4.79; S, 12.71. Found: C, 57.16; H, 4.47; S, 12.48. Ex-47C: 2-(4-Formyl-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid ethyl ester was prepared in an analogous fashion as described in Ex-29C using ethyl 2-bromoisobutyrate. Silica gel chromatography (ethyl acetate/hexanes, 1:1) gave the expected product as a solid (82%), mp 111–113° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.32 (s, 1H), 8.14 (s, 1H), 7.45 (dd, 1H, J=3.7, 1.3 Hz), 7.30 (dd, 1H, J=5.2, 1.3 Hz), 7.07 (dd, 1H, J=5.2, 3.7 Hz), 6.35 (s, 1H), 4.25 (q, 2H, J=7.2 Hz), 3.85 (s, 3H), 1.76 (s, 6H), 1.23 (t, 3H, J=7.2 Hz). MS (EI) m/z=348 ([M] + , 100%). Anal. Calcd. for C 18 H 20 O 5 S: C, 62.05; H, 5.79; S, 9.20. Found: C, 61.81; H, 5.81; S, 9.12. Ex-47D: To a solution of 2-(4-formyl-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid ethyl ester (0.29 g, 0.83 mmol) in a mixture of tetrahydrofuran, water and methanol (9 mL, 4:1:1) was added lithium hydroxide (0.10 g, 2.49 mmol) and the resulting yellow slurry was stirred at rt for 5 h. The mixture was diluted with water (5 mL) and extracted with ethyl acetate (1×5 mL). The aqueous layer was acidified with a 1 N HCl solution and extracted with ethyl acetate (3×15 mL). The combined organic layers was dried over sodium sulfate and concentrated to afford 0.13 g (87%) of 2-(4-formyl-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid as a pale green solid, mp 183–184° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.32 (s, 1H), 8.12 (s, 1H), 7.40 (d, 1H, J=3.6 Hz), 7.32 (d, 1H, J=4.8 Hz), 7.08 (dd, 1H, J=4.8, 3.6 Hz), 6.47 (s, 1H), 3.86 (s, 3H), 1.78 (s, 6H). MS (EI) m/z=320 ([M] + , 100%). Anal. Calcd. for C 16 H 16 O 5 S: C, 59.99; H, 5.03; S, 10.01. Found: C, 60.04; H, 5.26; S, 9.70. 2-(4-Formyl-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid (Ex-47, 0.23 g, 0.72 mmol) and 4-acetylbenzoic acid (0.12 g, 0.72 mmol) were dissolved in a dimethylformamide-methanol solution (5 mL, 7:3). After complete dissolution, lithium methoxide (0.11 g, 2.9 mmol) was added and the resulting orange slurry was stirred in the dark at room temperature for 4 h. Upon completion, as determined by HPLC, the mixture was diluted with water (15 mL), acidified with a 1 N hydrochloric acid solution, and extracted with ethyl acetate (4×25 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was taken up in a tetrahydrofuran-heptane solution (5 mL, 10:1) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. The resulting precipitate was collected on filter paper and dried in vacuo to yield 0.30 g (90%) of the title compound as a dark yellow solid, mp 135–137° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.32 (s, 1H), 8.23 (d, 2H, J=8.4 Hz), 8.10 (d, 2H, J=8.4 Hz), 7.99 (d, 2H, J=15.6 Hz), 7.71 (d, 1H, J=3.0 Hz), 7.54 (d, 1H, J=5.1 Hz), 7.14 (dd, 1H, J=5.1, 3.0 Hz), 6.49 (s, 1H), 3.85 (s, 3H), 1.69 (s, 6H). MS (ESI) m/z=467 ([M+H] + , 100%). Anal. Calcd. for C 25 H 28 O 8 S.EtOH: C, 63.27; H, 5.51; S, 6.26. Found: C, 63.40; H, 5.19; S, 6.38. Example 48 2-[3E-(4-Methoxy-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid The title compound was prepared by condensing 4-methoxy-3-(thiophen-2-yl)-benzaldehyde (Ex-41A) and 2-acetylbenzoic acid in a similar manner as described in Ex-3. Beige solid with green tint, mp 79–81° C., 44% yield. 1 H-NMR (DMSO-D 6 ) δ 8.07 (d, J=2 Hz, 1H), 7.91 (d, J=8 Hz, 1H), 7.73 (dd, J=2, 4 Hz, 1H), 7.67–7.70 (m, 2H), 7.63 (dd, J=2, 7 Hz, 1H), 7.57 (dd, J=2,5 Hz, 1H), 7.50 (d, J=8 Hz, 1H), 7.22 (d, J=2 Hz, 2H), 7.19 (d, J=8 Hz, 1H), 7.12 (dd, J=4, 5 Hz, 1H), 3.96 (s, 3H). HRMS m/z=calc. 365.0848, found 365.0853. Example 49 4-(3E-{2-Methoxy-4-[2-(2-methoxy-ethoxy)-ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic acid Ex-49A: To a solution of 4-hydroxy-2-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-47B, 0.50 g, 2.14 mmol) and tri(ethylene glycol) monomethyl ether (0.38 g, 3.2 mmol) in tetrahydrofuran (20 mL) was added triphenylphosphine (0.84 g, 3.2 mmol) and the resulting mixture was cooled to 0° C. Diethyl azodicarboxylate (0.55 g, 3.2 mmol) was then added drop wise, stirred at 0° C. for 30 min, and allowed to warm to rt. The solution was stirred for an additional 24 and concentrated under reduced pressure to a brown oil. Silica gel chromatography (ethyl acetate/hexanes, 8:1) afforded 0.31 g (45%) of the expected 2-methoxy-4-[2-(2-methoxy-ethoxy)-ethoxy]-5-thiophen-2-yl-benzaldehyde as a viscous clear oil. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.34 (s, 1H), 8.13 (s, 1H), 7.48 (d, 1H, J=3.6 Hz), 7.30 (t, 1H, J=5.1 Hz), 7.06 (dd, 1H, J=5.1, 3.6 Hz), 6.56 (s, 1H), 4.34 (t, 2H, J=5.1 Hz), 3.94 (t, 2H, J=5.1 Hz), 3.96 (s, 3H), 3.72–3.75 (m, 2H), 3.56–3.59 (m, 2H), 3.39 (s, 3H). MS (ESI) m/z=337 ([M+H] 30 , 100%). HRMS (EI) Calcd. for C 17 H 20 O 5 S: 336.1031. Found: 336.1028. The title compound was prepared by condensing 2-methoxy-4-[2-(2-methoxy-ethoxy)-ethoxy]-5-thiophen-2-yl-benzaldehyde (Ex-49A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 174–175° C., 61% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.28 (s, 1H), 8.23 (d, 2H, J=8.1 Hz), 8.05–8.11 (m, 3H), 7.91 (d, 1H, J=15.3 Hz), 7.72 (d, 1H, J=2.7 Hz), 7.52 (d, 1H, J=4.2 Hz), 7.11–7.15 (m, 1H), 6.86 (s, 1H), 4.39 (t, 2H, J=3.9 Hz), 3.99 (s, 3H), 3.89 (t, 2H, J=3.9 Hz), 3.64 (t, 2H, J=3.9 Hz), 3.48 (t, 2H, J=3.9 Hz), 3.25 (s, 3H). MS (ESI) m/z=483 ([M+H]+, 100%). Anal. Calcd. for C 26 H 26 O 7 S: C, 64.71; H, 5.43; S, 6.64. Found: C, 64.43; H, 5.34; S, 6.54. Example 50 4-{3E-[4-(3-Hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid Ex-50A: To a solution of 3-(tert-butyl-dimethyl-silanyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-propan-1-ol (25.0 g, 74.3 mmol) and triethylamine (22.6 g, 223 mmol) in dichloromethane (150 mL) at 0° C. was added mesyl chloride (12.8 g, 111 mmol) and the resulting slurry was stirred at 0° C. for 15 min and allowed to warm to rt. The solution was stirred for an additional 3 h at rt and diluted with water (130 mL) and ethyl acetate (350 mL). The layers were separated and the aqueous was extracted with ethyl acetate (1×150 mL). The combined organic extracts were washed with a saturated sodium bicarbonate (1×200 mL), a 50% sodium chloride solution (2×200 mL), dried over sodium sulfate and concentrated to afford 29.5 g (97%) of the expected methanesulfonic acid 3-(tert-butyl-dimethyl-silanyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-propyl ester as a yellow oil, 97% yield. 1 H-NMR (300 MHz, CDCl 3 ) δ 4.29 (d, 2H, J=5.7 Hz), 3.61–3.68 (m, 4H), 2.99 (s, 3H), 2.04–2.11 (m, 1H), 0.88 (s, 18H), 0.049 (s, 12H). HRMS (ESI) Calcd. for C 17 H 40 O 5 SSi 2 : 413.2213. Found 413.2226. Ex-50B: 4-[3-(tert-Butyldimethyl-silanyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-propoxy]-2-methoxy-5-thiophen-2-yl-benzaldehyde was prepared in an analogous fashion as described in EX-29C using methanesulfonic acid 3-(tert-butyl-dimethyl-silanyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-propyl ester (Ex-50A). Silica gel chromatography (ethyl acetate/hexanes, 1:6) gave the expected product as a pale green solid, 90% yield. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.34 (s, 1H), 8.13 (s, 1H), 7.41 (dd, 1H, J=3.6, 1.2 Hz), 7.28 (dd, J=5.1, 1.2 Hz), 7.05 (dd, 1H, J=5.1, 3.6 Hz), 6.54 (s, 1H), 4.22 (d, 2H, J=5.7 Hz), 3.96 (s, 3H), 3.80 (d, 4H, J=5.7 Hz), 2.33 (pentet, 1H, J=5.7 Hz), 0.88 (s, 18H), 0.012 (s, 12H). MS (ESI) m/z=551 ([M+H] + , 100%). HRMS (EI) Calcd. for C 28 H 46 O 5 SSi 2 : 550.2604. Found: 550.2593. Ex-50C: To a solution of 4-[3-(tert-butyl-dimethyl-silanyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-propoxy]-2-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-50B, 0.78 g, 1.41 mmol) in tetrahydrofuran (5 mL) was added tetrabutylammonium fluoride (1 M in tetrahydrofuran, 3.0 mL, 2.9 mmol) and the mixture was stirred at rt for 30 min. The reaction was diluted with ethyl acetate (50 mL) and washed with a 50% ammonium chloride solution (1×30 mL), water (2×30 mL), brine (1×30 mL), dried over sodium sulfate and concentrated to a crude yellow solid. Silica gel chromatography afforded 0.37 g (99%) of the expected 4-(3-hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-benzaldehyde as a pale yellow solid, 90% yield, mp 144–145° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.33 (s, 1H), 8.10 (s, 1H), 7.38 (dd, 1H, J=3.6, 1.5 Hz), 7.30 (dd, 1H, J=5.1, 1.5 Hz), 7.07 (dd, 1H, J=5.1, 3.6 Hz), 6.59 (s, 1H), 4.35 (d, 2H, J=6.0 Hz), 4.02 (t, 4H, J=4.8 Hz), 3.96 (s, 3H), 2.33 (pentet, 1H, J=6.0 Hz), 1.89 (t, 2H, J=4.8 Hz). MS (ESI) m/z=323 ([M+H] + , 100%). Anal. Calcd. for C 16 H 18 O 5 S: C, 59.61; H, 5.63; S, 9.95. Found: C, 59.34; H, 5.75; S, 9.82. The title compound was prepared by condensing 4-(3-hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-50C) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 199–201° C., 60% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.31 (s, 1H), 8.23 (d, 2H, J=8.7 Hz), 8.06–8.11 (m, 3H), 7.93 (d, 1H, J=15.0 Hz), 7.71 (d, 1H, J=3.3 Hz), 7.54 (d, 1H, J=5.1 Hz), 7.13–7.16 (m, 1H), 6.87 (s, 1H), 4.62 (brs, 2H), 4.27 (d, 2H, J=5.1 Hz), 4.00 (s, 3H), 3.62 (brs, 4H), 2.11–2.15 (m, 1H). MS (ESI) m/z=469 ([M+H] + , 100%). Anal. Calcd. for C 25 H 24 O 7 S.¼H 2 O: C, 63.48; H, 5.22; S, 6.78. Found: C, 63.45; H, 5.29; S, 6.61. Example 51 5-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid methyl ester Ex-51A: 5-(5-Formyl-2,4-dimethoxy-phenyl)-thiophene-2-carboxylic acid methyl ester was prepared-starting from 5-bromo-thiophene-2-carboxylic acid methyl ester in a similar manner as described in Ex-46A through -46D. Yellow solid, 18% yield. 1 H-NMR (CDCl 3 ) δ 10.32 (s, 1H), 8.16 (s, 1H), 7.74 (d, J=4.4 Hz, 1H), 7.42 (d, J=4.4 Hz, 1H), 6.51 (s, 1H), 4.05 (s, 3H), 3.98 (s, 3H), 3.90 (s, 3H). HRMS (ES+) Calcd. for C 15 H 14 O 5 S: 307.0640. Found: 307.0630. 4-Acetylbenzoic acid (24 mg, 0.15 mmol) and 5-(5-formyl-2,4-dimethoxy-phenyl)-thiophene-2-carboxylic acid methyl ester (Ex-51A, 46 mg, 0.15 mmol) were dissolved in DMF (4 mL). Lithium methoxide, 1M in methanol (0.29 mL) was added and the solution stirred at room temperature overnight. The reaction solution was poured into cold 1N HCl (3 mL) and extracted with EtOAc (3×20 mL); the organic phase was washed with brine (1×10 mL), dried over sodium sulfate, filtered, and concentrated. The resulting orange residue was purified via silica gel chromatography (0–10% MeOH/CH 2 Cl 2 ) to provide 89 mg of yellow solid which still contained DMF. The solid was slurried in EtOH for several hours, filtered, and dried to provide 31 mg of final product as a yellow solid (47% yield). 1 H-NMR (DMSO-d 6 ) δ 8.47 (s, 1H), 8.23 (d, J=9 Hz, 2H), 8.01–8.11 (m, 4H), 7.89 (d, J=4 Hz, 1H), 7.82 (d, J=4 Hz, 1H), 6.90 (s, 1H), 4.09 (s, 3H), 4.03 (s, 3H), 3.84 (s, 3H). HRMS (ES+) Calcd. for C 24 H 20 O 7 S: 453.1008. Found: 453.1020. Example 52 5-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid The title compound was prepared through routine hydrolysis of 5-{5-[3-(4-Carboxy-phenyl)-3-oxo-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid methyl ester (Ex-51). Orange solid, mp>260° C., 43% yield. 1 H-NMR (DMSO-d 6 ) δ 8.43 (s, 1H), 8.26 (d, J=8 Hz, 2H), 8.01–8.12 (m, 4H), 7.82 (d, J=4 Hz, 1H), 7.71 (d, J=4 Hz, 1H), 6.89 (s, 1H), 4.08 (s, 3H), 4.03 (s, 3H). Example 53 4-[3E-(4-Ethoxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-53A: Reaction of 4-hydroxy-2-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-47B) and (2-ethoxymethyl-5-hydroxymethyl-[1,3]dioxolan-4-yl)methanol was preformed under the Mitsunobu condition using triphenylphosphine and diethyl azodicarboxylate in THF. However, the expected product, 4-(2-ethoxymethyl-5-hydroxymethyl-[1,3]dioxolan-4-ylmethoxy)-2-methoxy-5-thiophen-2-yl-benzaldehyde, was not obtained. Instead, 4-ethoxy-2-methoxy-5-thiophen-2-yl-benzaldehyde was formed via cleavage of the cyclic ethyl orthoformate group under the reaction conditions. Silica gel chromatography (ethyl acetate/hexanes, 1:2) gave 0.16 g (90%) of 4-ethoxy-2-methoxy-5-thiophen-2-yl-benzaldehyde, mp 101–103° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.33 (s, 1H), 8.15 (s, 1H), 7.48 (d, 1H, J=3.6 Hz), 7.29 (d, 1H, J=5.2 Hz), 7.07 (dd, 1H, J=5.2, 3.6 Hz), 6.50 (s, 1H), 4.25 (q, 2H, J=7.2 Hz), 3.97 (s, 3H), 1.59 (t, 3H, J=7.2 Hz). MS (EI) m/z=262 ([M] + , 100%). HMRS (EI) Calcd. for C 14 H 14 O 3 S: 262.0664. Found: 262.0667. The title compound was prepared by condensing 4-ethoxy-2-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-53A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 210–212° C., 76% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.31 (s, 1H), 8.23 (d, 2H, J=9.0 Hz), 8.06–8.11 (m, 3H), 7.92 (d, 1H, J=16.2 Hz), 7.71 (d, 1H, J=3.9 Hz), 7.52 (d, 1H, J=5.1 Hz), 7.13 (dd, 1H, J=5.1, 3.9 Hz), 6.82 (s, 1H), 4.33 (q, 2H, J=6.1 Hz), 3.99 (s, 3H), 1.48 (t, 3H, J=6.1 Hz). MS (ESI) m/z=409 ([M+H] + , 100%). Anal. Calcd. for C 23 H 20 O 5 S.½H 2 O: C, 66.17; H, 5.07; S, 7.68. Found: C, 65.88; H, 5.24; S, 7.36. Example 54 4-[3E-(4-Hydroxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid 4-Hydroxy-2-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-47B, 0.30 g, 0.86 mmol) and 4-acetylbenzoic acid (0.13 g, 0.86 mmol) were dissolved in a dimethylformamide-methanol solution (6 mL, 7:3). After complete dissolution, lithium methoxide (0.12 g, 3.3 mmol) was added and the resulting red slurry was stirred in the dark at room temperature for 18 h. The mixture was diluted with water (15 mL), acidified with a 1 N hydrochloric acid solution, and extracted with ethyl acetate (4×25 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was subjected to silica gel chromatography (CH 2 Cl 2 :MeOH, 20:1) to yield an orange solid containing residual amounts of starting acid. The solid was taken up in ethyl alcohol (5 mL) to remove acid impurity and the resulting precipitate was collected on filter paper and dried in vacuo to yield 0.010 g (5%) of the title compound as an orange solid, mp 243° C. (dec). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.18–8.23 (m, 3H), 8.06–8.09 (m, 2H), 8.02 (s, 1H), 7.85 (d, 1H, J=15.6 Hz), 7.68 (d, 1H, J=3.6 Hz), 7.47 (d, 1H, J=5.1 Hz), 7.11 (dd, 1H, J=5.1, 3.6 Hz), 6.67 (s, 1H), 4.13 (s, 1H), 3.89 (s, 3H). MS (ESI) m/z=381 ([M+H] 30 , 100%). HRMS (ESI) Calcd. for C 21 H 16 O 5 S: 381.0796. Found: 381.0800. Example 55 4-[3E-(2,4-Dimethoxy-5-thiazol-2-yl-phenyl)-acryloyl]-benzoic acid Ex-55A: 2,4-Dimethoxy-5-thiazol-2-yl-benzaldehyde was prepared from 2-bromothiazole in a similar manner as described in Ex-46A through -46D. Off-white solid, 83% yield. 1 H-NMR (CDCl 3 ) δ 10.34 (s, 1H), 8.86 (s, 1H), 7.89 (d, J=3.6 Hz, 1H), 7.36 (d, J=3.6 Hz, 1H), 6.56 (s, 1H), 4.12 (s, 3H), 4.02 (s, 3H). HRMS m/z: calc. 249.0460, found 249.0461. The title compound was prepared by condensing 2,4-dimethoxy-5-thiazol-2-yl-benzaldehyde (Ex-55A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp>260° C., 65% yield. 1 H-NMR (DMSO-d 6 ) δ 13.33 (bs, 1H), 8.74 (s, 1H), 8.22 (d, J=8 Hz, 2H), 8.04–8.12 (m, 3H), 7.95 (d, J=2 Hz, 1H), 7.82 (d, J=16 Hz, 1H), 7.76 (d, J=3 Hz, 1), 6.94 (s, 1H), 4.14 (s, 3H), 4.05 (s, 1H). HRMS m/z=calc. 396.0906, found 396.0903. Example 56 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid, sodium salt To a solution of 4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid (5.77 g, 13.0 mmol) in tetrahydrofuran (50 mL) was added sodium methoxide (0.70 g, 12.3 mmol). The reaction mixture was allowed to stir for 2 hours at ambient temperature. The precipitate was then filtered, washed with tetrahydrofuran and dried in vacuo to give the title compound (5.13 g, 85%) as a yellow solid, mp>235° C. 1 H-NMR (DMSO-d 6 ) δ 8.35 (s, 1H), 8.08 (d, J=8.4 Hz, 2H), 8.00–7.89 (m, 4H), 7.82 (d, J=7.6 Hz, 1H), 7.35–7.29 (m, 4H), 6.85 (s, 1H), 4.02 (s, 3H), 3.99 (s, 3H). MS m/z=443 (M + , 100%). Example 57 2-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-pyrrole-1-carboxylic acid tert-butyl ester Ex-57A: 2-(5-Formyl-2,4-dimethoxy-phenyl)-pyrrole-1-carboxylic acid tert-butyl ester was prepared from pyrrole-1-carboxylic acid tert-butyl ester-2-boronic acid in a similar manner as described in Ex-3A, 81% yield. 1 H-NMR (CDCl 3 ) δ 10.32 (s, 1H), 7.76 (s, 1H), 7.31–7.33 (m, 1H), 6.43 (s, 1H), 6.22–6.24 (m, 1H), 6.14–6.16 (m, 1H), 3.98 (s, 3H), 3.85 (s, 3H), 1.40 (s, 9H), HRMS (EI) Calcd. for C 18 H 21 NO 5 : 331.1420. Found: 331.1421. The title compound was prepared by condensing 2-(5-formyl-2,4-dimethoxy-phenyl)-pyrrole-1-carboxylic acid tert-butyl ester (Ex-57A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 205–207° C., 6% yield. 1 H-NMR (DMSO-d 6 ) δ 8.19 (d, J=5 Hz, 2H), 8.00–8.10 (m, 3H), 7.87 (s, 1H), 7.80 (d, J=16 Hz, 1H), 7.27–7.28 (m, 1H), 6.71 (s, 1H), 6.22–6.23 (m, 1H), 6.14–6.16 (m, 1H), 3.96 (s, 3H), 3.79 (s, 3H), 1.29 (s, 9H). MS m/z=476 ([M−H] + ). HMRS (EI) calcd. for C 27 H 27 NO 7 : 477.1788; found: 477.1793. Example 58 4-[3E-(2-Hydroxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid 2-Hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-29B, 0.10 g, 0.43 mmol) and 4-acetylbenzoic acid (0.070 g, 0.43 mmol) were dissolved in a dimethylformamide-methanol solution (2.8 mL, 7:3). After complete dissolution, lithium methoxide (0.065 g, 1.7 mmol) was added and the resulting red slurry was stirred in the dark at room temperature for 18 h. The mixture was diluted with water (10 mL), acidified with a 1 N hydrochloric acid solution, and extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was taken up in ethyl alcohol (5 mL) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. Note: the compound appears to decompose with heating. The resulting precipitate was collected on filter paper and dried in vacuo to yield 0.025 g (15%) of the title compound as a dark yellow solid, mp 125° C. (dec). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.73 (s, 1H), 8.18–8.22 (m, 3H), 8.09 (d, 2H, J=8.1 Hz), 8.05 (s, 1H), 7.87 (d, 1H, J=14.7 Hz), 7.60 (d, 1H, J=3.0 Hz), 7.49 (d, 1H, J=4.2 Hz), 7.11 (dd, 1H, J=4.2, 3.0 Hz), 6.67 (s, 1H), 3.90 (s, 3H). MS (ESI) m/z=381 ([M+H] + , 100%). Anal. Calcd. for C 21 H 16 O 5 S.EtOH: C, 64.77; H, 5.20; S, 7.52. Found: C, 64.68; H, 5.00; S, 7.77. Example 59 4-{3E-[2-(1-Carboxy-1-methyl-ethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid Ex-59A: 2-(2-Formyl-5-methoxy-4-thiophen-2-yl-phenoxy)-2-methyl-propionic acid ethyl ester was prepared in an analogous fashion as described in Ex-29C using ethyl 2-bromoisobutyrate. Silica gel chromatography (ethyl acetate/hexanes, 1:2) gave the expected product as a dark yellow solid (97%), mp 87–88° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.37 (s, 1H), 8.14 (s, 1H), 7.45 (dd, 1H, J=3.6, 1.2 Hz), 7.30 (d, 1H, J=5.4 Hz), 7.07 (dd, 1H, J=5.1, 3.6 Hz), 6.42 (s, 1H), 4.25 (q, 2H, J=6.9 Hz), 3.90 (s, 3H), 1.72 (s, 6H), 1.26 (t, 3H, J=6.9 Hz). MS (ESI) m/z=349 ([M+H] + , 100%). Anal. Calcd. for C 18 H 20 O 5 S: C, 62.05; H, 5.79; S, 9.20. Found: C, 62.15; H, 5.82; S, 9.06. Ex-59B: 2-(2-Formyl-5-methoxy-4-thiophen-2-yl-phenoxy)-2-methyl-propionic acid was prepared in an analogous fashion as described in Ex-47D. The crude solid was dried in vacuo to afford the product as a pale yellow solid (98%), mp 187–188° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 9.33 (s, 1H), 7.99 (s, 1H), 7.47 (dd, 1H, J=3.6, 1.5 Hz), 7.37 (d, 1H, J=4.8 Hz), 7.11 (dd, 1H, J=4.8, 3.6 Hz), 6.67 (s, 1H), 4.00 (s, 3H), 1.75 (s, 6H). MS (ESI) m/z=321 ([M+H] + , 100%). Anal. Calcd. for C 16 H 16 O 5 S: C, 59.99; H, 5.03; S, 10.01. Found: C, 59.80; H, 5.12; S, 9.87. 2-(2-Formyl-5-methoxy-4-thiophen-2-yl-phenoxy)-2-methyl-propionic acid (Ex-59B, 0.12 g, 0.39 mmol) and 4-acetylbenzoic acid (0.064 g, 0.39 mmol) were dissolved in a dimethylformamide-methanol solution (2.7 mL, 7:3). After complete dissolution, lithium methoxide (0.060 g, 1.6 mmol) was added and the resulting bright orange slurry was stirred in the dark at room temperature for 2 h. Upon completion, as determined by HPLC, the mixture was diluted with water (15 mL), acidified with a 1 N hydrochloric acid solution, and extracted with ethyl acetate (3×15 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was taken up in ethyl alcohol (5 mL) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. The resulting precipitate was collected on filter paper and dried in vacuo to yield 0.15 g (85%) of the title compound as a dark yellow solid, mp 223–225° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.31 (s, 1H), 8.23 (d, 2H, J=8.1 Hz), 8.10 (d, 2H, J=8.1 Hz), 8.06 (s, 1H), 7.95 (d, 1H, J=16.2 Hz), 7.69 (d, 1H, J=3.0 Hz), 7.55 (d, 1H, J=5.1 Hz), 7.14 (dd, 1H, J=5.1, 3.0 Hz), 6.58 (s, 1H), 3.88 (s, 3H), 1.66 (s, 6H). MS (ESI) m/z=467 ([M+H] + , 100%). Anal. Calcd. for C 25 H 22 O 7 S.⅓H 2 O: C, 63.55; H, 4.84; S, 6.79. Found: C, 63.39; H, 5.02; S, 6.53. Example 60 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride Ex-60A: 4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-benzaldehyde was prepared in an analogous fashion as described in Ex-29C using 4-(2-chloroethyl)morpholine. Silica gel chromatography (80 to 100% ethyl acetate/hexanes then 5% methanol/methylene chloride) gave of the expected product as a off-white solid (81%). 1 H-NMR (300 MHz, CDCl 3 ) δ 10.36 (s, 1H), 8.12 (s, 1H), 7.44 (dd, 1H, J=3.6, 1.5 Hz), 7.30 (dd, 1H, J=5.1, 1.5 Hz), 7.07 (dd, 1H, J=5.1, 3.6 Hz), 6.53 (s, 1H), 4.27 (t, 2H, J=6.3 Hz), 4.00 (s, 3H), 3.72–3.76 (m, 4H), 2.89 (t, 2H, J=6.3 Hz), 2.60–2.63 (m, 4H). MS (ESI) m/z=348 ([M+H] + , 100%). HRMS (EI) Calcd. for C 18 H 21 NO 4 S: 347.1191. Found: 347.1188. 4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-benzaldehyde (Ex-60A, 0.15 g, 0.43 mmol) and 4-acetylbenzoic acid (0.071 g, 0.43 mmol) were dissolved in a dimethylformamide-methanol solution (3.0 mL, 7:3). After complete dissolution, lithium methoxide (0.065 g, 1.7 mmol) was added and the resulting bright orange slurry was stirred in the dark at room temperature for 2 h. Upon completion, as determined by HPLC, the mixture was diluted with water (10 mL), acidified with a 1 N hydrochloric acid solution, and extracted with an ethyl acetate:tetrahydrofuran mixture (1:1, 6×20 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude solid was slurried in ethyl alcohol (5 mL) to remove residual impurities and the resulting solid was collected on filter paper and dried in vacuo to yield 0.21 g (98%) of the title compound as a dark yellow solid, mp: 255° C. (dec). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.34 (s, 1H), 8.26 (d, 2H, J=8.7 Hz), 8.11 (d, 2H, J=8.7 Hz), 8.08 (s, 1H), 7.95 (d, 1H, J=15.9 Hz), 7.71 (d, 1H, J=3.3 Hz), 7.55 (d, 1H, J=4.5 Hz), 7.15 (dd, 1H, J=4.5, 3.3 Hz), 6.94 (s, 1H), 4.68 (brs, 2H), 4.04 (s, 3H), 3.98 (brs, 2H), 3.81–3.88 (brm, 2H), 3.70 (brs, 2H), 3.54–3.58 (brm, 2H), 3.29 (brs, 2H). MS (ESI) m/z=494 ([M+H] + , 100%). Anal. Calcd. for C 27 H 28 ClNO 6 S: C, 61.18; H, 5.32; Cl, 6.69; N, 2.64; S, 6.05. Found: C, 61.18; H, 5.41; Cl, 6.16; N, 2.73; S, 5.87. Example 61 4-{3E-[5-(1H-Indol-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid Ex-61A: 2-(5-Formyl-2,4-dimethoxy-phenyl)-indole-1-carboxylic acid tert-butyl ester (Ex-36A, 2.0 g, 5.2 mmol) was dissolved in 100 ml of THF, and Bu 4 NF (6.86 g, 26 mmol) was added. The reaction mixture was stirred at room temperature overnight. No reaction occured at this condition. Then, Bu 4 NF (6.86 g, 26 mmol) was added to the mixture, and the mixture was stirred at reflux for 4 days. The reaction was about 50% completion (HPLC). The reaction mixture was poured into CH 2 Cl 2 , and washed with water and brine. The organic phase was dried over MgSO 4 , and concentrated. The residue was purified by column chromatography (EtOAc: Hex, 2:1) to give 0.45 g (30%) of 5-(1H-indol-2-yl)-2,4-dimethoxy-benzaldehyde. 1 H-NMR (CDCl 3 ) δ 10.37 (s, 1H), 9.25 (br, 1H), 8.28 (s, 1H), 7.63 (d, J=8 Hz, 1H), 7.39 (d, J=8 Hz, 1H), 7.08–7.20 (m, 2H), 6.92 (d, J=2 Hz, 1H), 6.56 (s, 1H) 4.11 (s, 3H), 4.00 (s, 3H). HMRS (EI) calcd. for C 17 H 15 NO 3 : 281.1052; found: 281.1049. The title compound was prepared by condensing 5-(1H-indol-2-yl)-2,4-dimethoxy-benzaldehyde (Ex-61A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Red solid, mp 210–212° C., 66% yield. 1 H-NMR (Aceton-d 6 ) δ 10.53 (br, s, 1H), 8.32 (s, 1H), 8.14–8.21 (m, 5H), 7.89 (d, J=15 Hz, 1H), 7.52 (d, J=8 Hz, 1H), 7.38 (d, J=7 Hz, 1H), 6.97–7.07 (m, 3H), 6.87 (s, 1H), 4.07 (s, 3H), 4.02 (s, 3H), MS m/z=427 ([M] + ). HMRS (EI) calcd. for C 26 H 21 NO 5 : 427.1420; found: 427.1435. Example 62 4-{3E-[2-(3,5-Dimethyl-isoxazol-4-ylmethoxy)-4-methoxy-5-thiolphen-2-yl-phenyl]-acryloyl}-benzoic acid Ex-62A: 2-(3,5-Dimethyl-isoxazol-4-ylmethoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-29C using 4-chloromethyl-3,5-dimethyl-isoxazole. 1 H-NMR (CDCl 3 ) δ 10.26 (s, 1H), 8.14 (s, 1H), 7.45 (d, J=6 Hz, 1H), 7.32 (d, J=5 Hz, 1H), 7.07–710 (m, 1H), 6.58 (s, 1H), 4.96 (s, 2H), 4.04 (s, 3H), 2.46 (s, 3H), 2.32 (s, 3H). The title compound was prepared by condensing 2-(3,5-dimethyl-isoxazol-4-ylmethoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-62A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 213–215° C. 1 H-NMR (CDCl 3 ) δ 8.20 (d, J=9 Hz, 2H), 7.88–8.03 (m, 4H), 7.58 (d, J=16 Hz, 1H), 7.44 (d, J=4 Hz, 1H), 7.34 (d, J=5 Hz, 1H), 7.12 (dd, J=4, 5 Hz, 1H), 6.63 (s, 1H), 4.97 (s, 2H), 4.01 (s, 3H), 2.46 (s, 3H), 2.34 (s, 3H). MS m/z=490 ([M+H] + ). HRMS (ES+) Calcd. for C 27 H 22 NO 6 S: 490.1324. Found: 490.1321. Example 63 4-[3E-(2-Pyrrolidin-1-yl-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-63A: A solution of 2-fluoro-5-thiophen-2-yl-benzaldehyde (1.42 g, 6.89 mmol) in pyrrolidine was refluxed (10 mL). After 4.5 days the reaction mixture was cooled and diluted with ethyl acetate. The solution of ethyl acetate was washed with hydrochloric acid (0.5M) sodium carbonate (2M) and saturated solution of sodium bicarbonate, dried over sodium sulfate, and concentrated. The crude product was purified by flash chromatography. Elution with ethyl acetate (20%, v/v, in hexane) afforded 2-pyrrolidin-1-yl-5-thiophen-2-yl-benzaldehyde (0.5 g, 32%). 1 H NMR (CDCl 3 ) δ 10.14 (s, 1H), 7.94 (d, J=2 Hz, 1H), 7.62 (dd, J=2.7, 9 Hz, 1H), 7.22–7.20 (m, 2H), 7.07–7.04 (m, 1H), 6.86 (d, J=9 Hz, 1H), 3.41 (m, 4H), 2.01 (m, 4H). The title compound was prepared by condensing 2-pyrrolidin-1-yl-5-thiophen-2-yl-benzaldehyde (Ex-63A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Red solid, mp 208–209° C. 1 H-NMR (DMSO-d 6 ) δ 12.50 (bs, 1H), 8.22 (d, J=8.5 Hz, 2H), 8.09–7.99 (m, 4H), 7.73 (d, J=15.5 Hz, 1H), 7.52–7.41 (m, 3H), 7.10–7.07 (m, 1H), 6.93 (d, J=9.0 Hz, 1H), 3.28 (m, 4H), 1.87 (m, 4H). Example 64 4-{3E-[2-(3-Hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid Ex-64A: To a solution of 2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde (10.0 g, 42.7 mmol) in N,N-dimethylformamide (100 mL) was added potassium carbonate (11.8 g, 85.4 mmol) and the resulting yellow slurry was heated to 80° C. Once at 80° C., methanesulfonic acid 3-(tert-butyl-dimethyl-silanyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-propyl ester (Ex-50A, 19.5 g, 46.9 mmol) was added dropwise and the reaction was stirred for an additional 24 h at 80° C. and cooled to room temperature. The mixture was diluted with water (500 mL) and extracted with ethyl acetate (3×150 mL). The combined organic layers was sequentially washed with a saturated sodium bicarbonate solution (1×150 mL), water (1×150 mL), and brine (1×150 mL), dried over sodium sulfate, and concentrated to a brown oil. Silica gel chromatography (100% ethyl acetate to 10% ethyl acetate/hexanes) gave 19.0 g (81%) of 2-[3-(tert-butyl-dimethyl-silanyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-propoxy]-4-methoxy-5-thiophen-2-yl-benzaldehyde as an off-white solid, mp 91–92° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.37 (s, 1H), 8.12 (s, 1H), 7.44 (dd, 1H, J=3.6, 1.2 Hz), 7.29 (d, 1H, J=5.1 Hz), 7.07 (dd, 1H, J=5.1, 3.6 Hz), 6.54 (s, 1H), 4.19 (d, 2H, J=6.0 Hz), 3.99 (s, 3H), 3.72–3.82 (m, 4H), 2.28 (pentet, 1H, J=6.0 Hz), 0.88 (s, 18H), 0.048 (s, 12H). MS (EI) m/z=550 ([M] + , 100%). Anal. Calcd. for C 28 H 46 O 5 SSi 2 : C, 61.05; H, 8.42; S, 5.82. Found: C, 61.20; H, 8.74; S, 5.69. Ex-64B: 2-(3-Hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde was prepared in an analogous fashion as described in Ex-50C. Silica gel chromatography (ethyl acetate/hexanes, 1:9) gave the expected product as an off-white solid. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.17 (s, 1H), 8.03 (s, 1H), 7.43 (dd, 1H, J=3.6, 1.2 Hz), 7.31 (d, 1H, J=5.1 Hz), 7.08 (dd, 1H, J=5.1, 3.6 Hz), 6.58 (s, 1H), 4.32 (d, 2H, J=6.0 Hz), 4.01 (s, 3H), 3.95–3.99 (m, 4H), 2.51 (t, 2H, J=5.1 Hz), 2.33 (pentet, 1H, J=5.4 Hz). MS (EI) m/z=322 ([M] + , 100%). HRMS (EI) Calcd. for C 16 H 18 O 5 S: 322.0875. Found: 322.0873. The title compound was prepared by condensing 2-(3-hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-64B) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Light orange solid, mp 219–220° C., 61% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.36 (s, 1H), 8.20 (d, 2H, J=7.5 Hz), 8.05–8.11 (m, 3H), 7.93 (d, 1H, J=16.2 Hz), 7.67 (d, 1H, J=3.0 Hz), 7.52 (d, 1H, J=5.1 Hz), 7.13 (dd, 1H, J=5.1, 3.0 Hz), 6.88 (s, 1H), 4.66 (brs, 2H), 4.23 (d, 2H, J=6.3 Hz), 4.01 (s, 3H), 3.55–3.66 (m, 4H), 2.09–2.14 (m, 1H). MS (ESI) m/z=469 ([M+H] + , 100%). Anal. Calcd. for C 25 H 24 O 7 S.H 2 O: C, 61.72; H, 5.39; S, 6.59. Found: C, 61.93; H, 5.30; S, 7.06. Example 65 4-{3E-[2-(3-Morpholin-4yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride Ex-65A: 2-(3-Morpholin-4-yl-propoxy)-5-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-60A, 80% yield. 1 H-NMR (DMSO-D6) δ 10.36 (s, 1H), 7.90 (dd, J=3, 5 Hz, 1H), 7.82 (d, 1H), 7.48 (d, 1H), 7.44 (d, 1H), 7.25 (d, 1H), 7.09 (t, 1H), 4.18 (t, 2H), 3.53 (m, 4H), 3.28 (br s, 2H), 2.43 (m, 4H), 1.89 (q, 2H). The title compound was prepared by condensing 2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-benzaldehyde (Ex-65A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 67% yield, mp 234–236° C. 1 H-NMR (DMSO-d6) δ 13.32 (br s, 1H), 11.10 (br s, 1H), 8.21 (m, 3H), 8.02 (m, 3H), 7.67 (dd, J=2,2 Hz, 1H), 7.56 (d, 1H), 7.50 (d, 1H), 7.14 (m, 2H), 4.21 (t, 2H), 3.86 (m, 4H), 3.23 (m, 6H), 2.29 (q, 2H). MS m/z=478 ([M+H] + , 100%). Anal. calculated for C 27 H 28 ClNO 5 S.3/2H 2 O: C, 59.94; H, 5.78; S, 5.93; found C, 60.20; H, 5.65; S, 5.94 Example 66 4-{3E-[4-Methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride Ex-66A: 4-Methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-60A, 78% yield. 1 H-NMR (DMSO-D6) δ 10.21 (s, 1H), 7.88 (s, 1H), 7.46 (m, 2H), 7.06 (t, 1H), 6.82 (s, 1H), 4.24 (t, 2H), 4.00 (s, 3H), 3.53 (m, 4H), 3.28 (m, 2H), 2.34 (m, 4H), 1.93 (q, 2H). The title compound was prepared by condensing 4-methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-benzaldehyde (Ex-66A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 72% yield, mp 188–191° C. (dec). 1 H-NMR (DMSO-d6) δ 12.63 (br s, 1H), 11.08 (br s, 1H), 8.33 (s, 1H), 8.22 (d, 2H), 8.05 (m, 3H), 7.89 (d, 1H), 7.65 (d, 1H), 7.49 (d, 1H), 7.10 (t, 1H), 6.84 (s, 1H), 4.30 (t, 2H), 3.98 (s, 3H), 3.84 (m, 4H), 3.21 (m, 6H), 2.28 (q, 2H). MS m/z=508 ([M+H] + , 100%). Anal. calculated for C 28 H 32 ClNO 7 S.H 2 O: C, 59.83; H, 5.74; S, 5.70; found C, 59.69; H, 5.80; S: 5.55. Example 67 4-[3E-(2-Dimethylcarbamoylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-67A: 2-(2-Formyl-5-methoxy-4-thiophen-2-yl-phenoxy)-N,N-dimethyl-acetamide was prepared in an analogous fashion as described in Ex-29C using 2-chloro-N,N-dimethylacetamide. Methylene chloride was used in place of ethyl acetate for the work up procedure. The crude solid was slurried in ethyl acetate (25 mL) to remove residual impurities. The resulting solid was collected on filter paper and dried in vacuo to give the expected product as a pale yellow solid (85%), mp 197–198° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.38 (s, 1H), 8.13 (s, 1H), 7.44 (d, 1H, J=3.6 Hz), 7.30 (dd, 1H, J=5.1, 1.8 Hz), 7.07 (dd, 1H, J=5.1, 3.6 Hz), 6.73 (s, 1H), 4.89 (s, 2H), 3.99 (s, 3H), 3.15 (s, 3H), 2.99 (s, 3H). MS (EI) m/z=319 ([M] + , 100%). Anal. Calcd. for C 16 H 17 NO 4 S.⅕H 2 O: C, 59.50; H, 5.43; N, 4.34; S, 9.93. Found: C, 59.65; H, 5.42; N, 4.40; S, 9.69. The title compound was prepared by condensing 2-(2-formyl-5-methoxy-4-thiophen-2-yl-phenoxy)-N,N-dimethyl-acetamide (Ex-67A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 228–229° C., 75% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.31 (d, 2H, J=9.3 Hz), 8.22 (d, 2H, J=13.3 Hz), 8.08 (d, 2H, J=9.3 Hz), 7.95 (s, 1H), 7.65 (d, 1H, J=2.7 Hz), 7.52 (d, 1H, J=5.1 Hz), 7.13 (dd, 1H, J=5.1, 2.7 Hz), 6.85 (s, 1H), 5.11 (s, 2H), 3.99 (s, 3H), 3.06 (s, 3H), 2.93 (s, 3H). MS (EI) m/z=465 ([M] + , 100%). HRMS (EI) Calcd. for C 25 H 23 NO 6 S: 465.1246. Found: 465.1246. Example 68 4-[3E-(4-Methoxy-2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-68A: Methanesulfonic acid 2-[2-(2-methoxy-ethoxy)-ethoxy]-ethyl ester was prepared in an analogous fashion as described in Ex-50A using di(ethylene glycol) methyl ether. The crude orange oil was dried in vacuo to give the expected product (oil) and was used without any further purification (99%). 1 H-NMR (300 MHz, CDCl 3 ) δ 4.37–4.40 (m, 2H), 3.76–3.78 (m, 2H), 3.61–3.70 (m, 6H), 3.53–3.57 (d, 2H), 3.38 (s, 3H), 3.08 (s, 3H). MS (ESI) m/z=243 ([M+H] + , 100%). HRMS (ESI) Calcd. for C 8 H 18 O 6 S: 243.0902. Found: 243.0914. Ex-68B: 4-Methoxy-2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-5-thiophen-2-yl-benzaldehyde was prepared in an analogous fashion as as described in Ex-29C using methanesulfonic acid 2-[2-(2-methoxy-ethoxy)-ethoxy]-ethyl ester (Ex-68A). Silica gel chromatography (ethyl acetate/hexanes, 8:1) gave the expected product as a pale yellow oil (70%). 1 H-NMR (300 MHz, CDCl 3 ) δ 10.38 (s, 1H), 8.12 (s, 1H), 7.44 (d, 1H, J=3.6 Hz), 7.30 (d, 1H, J=5.4 Hz), 7.07 (dd, 1H, J=5.4, 3.6 Hz), 6.57 (s, 1H), 4.31 (t, 2H, J=4.8 Hz), 3.99 (s, 3H), 3.94 (t, 2H, J=4.8 Hz), 3.74–3.78 (m, 2H), 3.62–3.69 (m, 4H), 3.53–3.56 (m, 2H), 3.37 (s, 3H). MS (EI) m/z=380 ([M] + , 100%). HRMS (ESI) Calcd. for C 8 H 18 O 6 S: 243.0902. Found: 243.0914. The title compound was prepared by condensing 4-methoxy-2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-5-thiophen-2-yl-benzaldehyde (Ex-68B) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 137–138° C., 82% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.20–8.23 (m, 3H), 8.09 (d, 2H, J=8.3 Hz), 8.01 (m, 2H), 7.66 (d, 1H, J=3.6 Hz), 7.52 (d, 1H, J=5.1 Hz), 7.13 (dd, 1H, J=5.1, 3.6 Hz), 6.88 (s, 1H), 4.37 (t, 2H, J=3.6 Hz), 4.01 (s, 3H), 3.89 (t, 2H, J=3.6 Hz), 3.64–3.67 (m, 2H), 3.53–3.56 (m, 2H), 3.47–3.50 (m, 2H), 3.36–3.95 (m, 2H), 3.19 (s, 3H). MS (ESI) m/z=527 ([M+H] + , 100%). Anal. Calcd. for C 28 H 30 O 8 S: C, 63.86; H, 5.74; S, 6.09. Found: C, 64.08; H, 5.77; S, 6.09. Example 69 4-{3E-[2,4-Dimethoxy-5-(2-methyl-thiazol-4-yl)-phenyl]-acryloyl}-benzoic acid Ex-69A: A solution of 2-bromo-1-(3,4-dimethoxy-phenyl)-ethanone (0.62 g, 2.39 mmol) and thioacetamide (0.18 g, 2.39 mmol) in ethanol (30 mL) was refluxed for 2 hours and the solvent was removed under reduced pressure. The product, 4-(3,4-dimethoxy-phenyl)-2-methyl-thiazole (0.56 g, 100%) was obtained as a white solid and used without further purification. To a suspension of 4-(3,4-dimethoxy-phenyl)-2-methyl-thiazole obtained above (0.70 g, 2.97 mmol) in dichloromethane (60 mL) at 0° C. was added dichloromethyl methyl ether (0.40 mL, 4.46 mmol) followed by addition of titanium tetrachloride (1.0 M solution in dichloromethane, 8.9 mL, 8.9 mmol) dropwise. The reaction mixture was allowed to stir overnight at ambient temperature and then poured into ice. The aqueous solution was extracted with dichloromethane. The solution of dichloromethane was washed with hydrochloric acid (0.5M), saturated solution of sodium bicarbonate and brine, dried over sodium sulfate and concentrated. The product, 2,4-dimethoxy-5-(2-methyl-thiazol-4-yl)-benzaldehyde, was obtained as a white solid. 1 H NMR (CDCl 3 ) δ 10.33 (s, 1H), 8.67 (s, 1H), 7.56 (s, 1H), 6.52 (s, 1H), 4.03 (s, 3H), 3.99 (s, 3H), 2.75 (s, 3H). The title compound was prepared by condensing 2,4-dimethoxy-5-(2-methyl-thiazol-4-yl)-benzaldehyde (Ex-69A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 201–202° C. (dec.). 1 H-NMR (DMSO-d 6 ) δ 8.47 (s, 1H), 8.14–7.97 (m, 5H), 7.76 (s, 1H), 7.65 (d, J=15.8 Hz, 1H), 6.81 (s, 1H), 4.00 (s, 3H), 3.98 (s, 3H), 2.69 (s, 3H). MS m/z=409 (M + , 70%), 378 ([M−OCH 3 ] + , 100%). Example 70 4-{3E-[5-(1H-Benzoimidazol-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid Ex-70A: A solution of benzene-1,2-diamine (2.60 g, 24.1 mmol) and 2,4-dimethoxy-benzaldehyde (4.0 g, 24.1 mmol) in ethanol (60 mL) containing catalytic amount of acetic acid was refluxed overnight. Solvent was then evaporated under reduced pressure. The residue oil was triturated in ethyl acetate to obtain 2-(2,4-dimethoxy-phenyl)-1H-benzoimidazole (0.76 g, 12%). The crude product was used without further purification. To a solution of 2-(2,4-dimethoxy-phenyl)-1H-benzoimidazole obtained above (0.76 g, 2.99 mmol) in dichloromethane (20 mL) was added dichloromethyl methyl ether (0.41 mL, 4.48 mmol) followed by addition of titanium tetrachloride (1.0M in dichloromethane, 9.0 mL, 9.0 mmol) at 0° C. The reaction mixture was allowed to stir overnight at ambient temperature and then poured into ice. A solution of sodium hydroxide (5M) was added dropwise until the pH of the solution was about 12. The basic solution was extracted with dichloromethane. The combined solution of dichloromethane was subsequently washed with brine, dried over sodium carbonate and concentrated. The product, 5-(1H-benzoimidazol-2-yl)-2,4-dimethoxy-benzaldehyde (0.40 g, 47%), was obtain and used without further purification. 1 H NMR (CDCl 3 ) δ 10.32 (s, 1H), 10.27 (bs, 1H), 9.03 (s, 1H), 7.83 (d, J=9 Hz, 1H), 7.48–7.45 (m, 1H), 7.31–7.22 (m, 1H), 6.58 (s, 1H), 4.18 (s, 3H), 4.01 (s, 3H). MS m/z=282 (M + , 100%). The title compound was prepared by condensing 5-(1H-benzoimidazol-2-yl)-2,4-dimethoxy-benzaldehyde (Ex-70A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp>240° C. (dec.). 1 H-NMR (DMSO-d 6 ) δ 8.72 (s, 1H), 12.10 (s, 1H), 8.18 (d, J=8.4 Hz, 2H), 8.08–8.02 (m, 3H), 7.80 (d, J=15.4 Hz, 1H), 7.59 (s, 2H), 7.17–7.13 (m, 2H), 6.89 (s, 1H), 4.10 (s, 3H), 4.03 (s, 3H). MS m/z=429 ([M+H] + , 100%). Example 71 4-[3E-(2-Carbamoylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid Ex-71A: 2-(2-Formyl-5-methoxy-4-thiophen-2-yl-phenoxy)-acetamide was prepared in an analogous fashion as described in Ex-29C using 2-bromoacetamide. Silica gel chromatography (ethyl acetate/hexanes, 8:1) gave the expected product as a pale yellow solid (75%), mp: 178–179° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.05 (s, 1H), 7.99 (s, 1H), 7.67 (brs, 1H), 7.44 (d, 1H, J=3.6 Hz), 7.34 (d, 1H, J=5.4 Hz), 7.10 (dd, 1H, J=5.4, 3.6 Hz), 6.48 (s, 1H), 5.67 (brs, 1H), 4.64 (s, 2H), 4.02 (s, 3H). MS (EI) m/z=291 ([M] + , 100%). Anal. Calcd. for C 14 H 13 NO 4 S: C, 57.72; H, 4.50; N, 4.81; S, 11.01. Found: C, 57.63; H, 4.50; N, 4.87; S, 11.03. The title compound was prepared by condensing 2-(2-formyl-5-methoxy-4-thiophen-2-yl-phenoxy)-acetamide (Ex-71A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 70% yield, mp 235° C. (dec.). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.26–8.30 (m, 3H), 8.08–8.11 (m, 4H), 7.67 (d, 1H, J=2.7 Hz), 7.65 (brs, 1H), 7.53 (d, 1H, J=4.0 Hz), 7.49 (brs, 1H), 7.13 (m, 1H), 6.77 (s, 1H), 4.75 (s, 2H), 3.97 (s, 3H). MS (EI) m/z=437 ([M] + , 100%). HRMS (EI) Calcd. for C 23 H 19 NO 6 S: 437.0933. Found: 437.0924. Example 72 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-2-oxo-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid Ex-72A: 4-Methoxy-2-(2-morpholin-4-yl-2-oxo-ethoxy)-5-thiophen-2-yl-benzaldehyde was prepared in an analogous fashion as described in Ex-29C using 4-(2-chloroacetyl)morpholine. Silica gel chromatography (80% ethyl acetate/hexanes to 100% ethyl acetate) gave the expected product as a pale yellow solid, mp 200–201° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.33 (s, 1H), 8.12 (s, 1H), 7.44 (d, 1H, J=3.6 Hz), 7.31 (d, 1H, J=5.1 Hz), 7.08 (dd, 1H, J=5.1, 3.6 Hz), 6.74 (s, 1H), 4.89 (s, 2H), 4.00 (s, 3H), 3.67 (brs, 8H). MS (ESI) m/z=362 ([M+H] + , 100%). Anal. Calcd. for C 18 H 19 NO 5 S: C, 59.82; H, 5.30; N, 3.88; S, 8.87. Found: C, 59.88; H, 5.36; N, 3.90; S, 8.75. The title compound was prepared by condensing 4-methoxy-2-(2-morpholin-4-yl-2-oxo-ethoxy)-5-thiophen-2-yl-benzaldehyde (Ex-72A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Orange solid, mp 231–233° C., 70% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.28–8.35 (m, 3H), 8.21 (s, 1H), 8.07–8.11 (m, 3H), 7.66 (d, 1H, J=3.3 Hz), 7.52 (d, 1H, J=5.1 Hz), 7.13 (dd, 1H, J=5.1, 3.3 Hz), 6.87 (s, 1H), 5.13 (s, 2H), 4.00 (s, 3H), 3.65 (brm, 4H), 3.54–3.55 (m, 4H). MS (EI) m/z=507 ([M] + , 100%). Anal. Calcd. for C 27 H 25 NO 7 S.½EtOH: C, 63.55; H, 5.61; N, 2.60; S, 5.95. Found: C, 63.13; H, 5.55; N, 2.53; S, 5.84. Example 73 4-(3E-{4-Methoxy-2-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic acid, hydrochloride Ex-73A: Methanesulfonic acid 2-(1-methyl-pyrrolidin-2-yl)-ethyl ester was prepared in an analogous fashion as described in Ex-50A using (S)-(−)-1-methyl-2-pyrrolidinemethanol. The crude orange oil was dried in vacuo to give the expected product and was used without any further purification (40%). 1 H-NMR (300 MHz, CDCl 3 ) δ 4.99–5.04 (m, 1H), 4.41–4.51 (m, 1H), 4.19–4.29 (m, 1H), 3.88–3.94 (m, 1H), 3.49 (s, 3H), 3.17–3.29 (m, 1H), 2.95–3.05 (m, 1H), 2.74 (s, 3H), 2.41–2.58 (m, 3H), 1.98–2.08 (m, 2H). MS (EI) m/z=207 ([M] + , 100%). HRMS (EI) Calcd. for C 18 H 19 NO 5 S: 207.0929. Found: 207.0922. Ex-73B: 4-Methoxy-2-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-5-thiophen-2-yl-benzaldehyde was prepared in an analogous fashion as described in Ex-29C using Methanesulfonic acid 2-(1-methyl-pyrrolidin-2-yl)-ethyl ester (Ex-73A). Silica gel chromatography (10% methanol/methylene chloride to 15% methanol/methylene chloride) gave 0.50 g (70%) of the expected product as a pale yellow oil. 1 H-NMR (300 MHz, CDCl 3 , major isomer) δ 10.35 (s, 1H), 8.09 (s, 1H), 7.42–7.44 (m, 1H), 7.30 (d, 1H, J=5.1 Hz), 7.06–7.09 (m, 1H), 6.49 (s, 1H), 4.80 (m, 1H), 4.20–4.26 (m, 1H), 3.98 (s, 3H), 2.64–2.84 (m, 2H), 2.47 (s, 3H), 1.80–2.33 (m, 7H). MS (EI) m/z=345 ([M] + , 100%). HRMS (EI) Calcd. for C 18 H 19 NO 5 S: 345.1399. Found: 345.1401. The title compound was prepared by condensing 4-methoxy-2-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-5-thiophen-2-yl-benzaldehyde (Ex-73B) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Dark Yellow solid, 52%, mp 206–208° C. 1 H-NMR (300 MHz, DMSO-d 6 , major isomer) δ 8.30 (s, 1H), 8.25 (d, 2H, J=7.8 Hz), 8.07–8.12 (m, 3H), 7.94 (d, 1H, J=15.6 Hz), 7.68 (d, 1H, J=3.3 Hz), 7.52 (d, 1H, J=5.1 Hz), 7.14 (dd, 1H, J=5.1, 3.3 Hz), 6.86 (s, 1H), 5.05 (m, 1H), 4.34 (m, 1H), 4.00 (s, 3H), 3.40–3.46 (m, 2H), 2.81 (s, 3H), 2.40–2.44 (m, 1H), 2.16–2.27 (m, 2H), 1.81–2.00 (m, 4H). MS (ESI) m/z=492 ([M+H] + , 100%). Anal. Calcd. for C 28 H 30 ClNO 5 S.½H 2 O: C, 60.59; H, 5.99; N, 2.52; S, 5.78. Found: C, 60.70; H, 5.85; N, 2.64; S, 6.15. Example 74 4-{3E-[2,4-Dimethoxy-5-(1H-pyrazol-4-yl)-phenyl]-acryloyl}-benzoic acid Ex-74A: A solution of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.33 g, 1.70 mmol) and di-tert-butyl dicarbonate (0.51 g, 2.34 mmol) in dichloromethane (10 mL) was allowed to stir overnight at ambient temperature. The solution was then washed with saturated solution of sodium bicarbonate and brine, dried over sodium sulfate, and concentrated. The crude product of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (0.61 g) was used in next step without further purification. Ex-74B: To a mixture of 2,4-dimethoxy-5-bromo-benzaldehye (0.28 g, 1.13 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (Ex-76A, 0.61 g, 1.70 mmol), bis(tri-tert-butylphosphine)palladium (43 mg, 0.085 mmol) and potassium fluoride (0.24 g, 4.08 mmol) was added degassed tetrahydrofuran (15 mL). The reaction mixture was heated at 60° C. for one day. Additional potassium fluoride (0.24 g, 4.08 mmol) and water (20 μL) were added. The reaction mixture continued to stir at 60° C. for another 8 hours. The reaction was then quenched by water. The aqueous solution was extracted with ethyl acetate. The solution of ethyl acetate was washed with saturated solution of sodium bicarbonate, brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography. Elution with ethyl acetate (50%, v/v, in hexane) afforded 4-(5-formyl-2,4-dimethoxy-phenyl)-pyrazole-1-carboxylic acid tert-butyl ester (0.15 g, 40%) as white solid. 1 H NMR (CDCl 3 ) δ 10.35 (s, 1H), 8.43 (s, 1H), 8.09 (s, 1H), 8.02 (s, 1H), 6.52 (s, 1H), 4.02 (s, 3H), 3.99 (s, 3H), 1.68 (s, 9H). MS m/z=333 ([M+H] + , 100%). The title compound was prepared by condensing 2,4-dimethoxy-5-(1H-pyrazol-4-yl)-benzaldehyde (Ex-74B) and 4-acetylbenzoic acid in a similar manner as described in Ex-3 including an acid work-up. Yellow solid, mp>250° C. 1 H-NMR (DMSO-d 6 ) δ 12.42 (bs, 1H), 8.20–8.03 (m, 8H), 7.85 (d, J=16.1 Hz), 6.74 (s, 1H), 3.95 (s, 3H), 3.94 (s, 3H). MS m/z=379 ([M+H] + , 100%). Example 75 4-{3E-[2,4-Dimethoxy-5-(2H-tetrazol-5-yl)-phenyl]-acryloyl}-benzoic acid Ex-75A: A solution of 2-(5-bromo-2,4-dimethoxy-phenyl)-[1,3]dioxolane (Ex-46A, 1.16 g, 4.9 mmol), sodium azide (641.3 mg, 9.86), and zinc bromide (552.2 mg, 2.46 mmol) in water (14 mL) and isopropanol (17 mL) were mixed and refluxed for 18 hours. The reaction mixture was quenched with 3N HCl (60 mL) and extracted with ethyl acetate (2×75 mL). The organic was concentrated to a white solid. The solid was stirred in 0.25N NaOH (100 mL) for one hour. The suspension was filtered and the filtrate was collected and acidified with 1N HCl to a pH of 2. The aqueous solution was extracted with ethyl acetate:THF (40%). The organics were collected and concentrated to a crude brown solid of 2,4-dimethoxy-5-(2H-tetrazol-5-yl)-benzaldehyde (77.8 mg, 7%). 1 H-NMR (DMSO-d6) δ 10.09 (s, 1H), 7.97 (s, 1H), 6.89 (s, 1H), 4.04 (s, 3H), 4.02 (s, 3H). MS m/z=234 ([M] + , 94%), 191 (100%). The title compound was prepared by condensing 2,4-dimethoxy-5-(2H-tetrazol-5-yl)-benzaldehyde (Ex-75A) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, 19% yield, mp 218° C. (dec). 1 H-NMR (DMSO-d6) δ 8.58 (s, 1H), 8.20 (d, 2H), 8.03 (m, 3H), 7.85 (d, 1H), 6.90 (s, 1H), 4.04 (s, 3H), 4.02 (s, 3H). MS m/z=422 ([M+CH 3 CN+H] + , 100%). HRMS m/z: calc. 381.1199, found 381.1184. Example 76 4-{3E-[5-(3H-Imidazo[4,5-b]pyridin-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid Ex-76A: To a suspension of 2,4-dimethoxybenzoic acid (0.36 g, 2 mmol) and 8 ml of POCl 3 in a 50 ml of a round-bottom flask, 2,3-diaminopyridine (0.22 g, 2 mmol) was added. The mixture was heated to reflux for 4 hours and then cooled to room temperature. The reaction mixture was then concentrated to remove most of the POCl 3 . The residue was carefully treated with 1N HCl at 0° C. using a water-ice bath, then neutralized with NaOH (50%). The off-white solid was filtered to give 2-(2,4-dimethoxy-phenyl)-3H-imidazo[4,5-b]pyridine (0.44 g, 88%). 1 H-NMR (DMSO-d 6 ) δ 8.28–8.36 (m, 2H), 7.97 (d, J=8 Hz, 1H), 7.21–7.25 (m, 1H), 6.80 (s, 1H), 6.78 (d, J=9 Hz, 1H), 4.05 (s, 3H), 3.91 (s, 3H). HRMS (ES+) Calcd. for C 24 H 19 N 3 O 5 : 430.1403. Found: 430.1414. Ex-76B: To a suspension of 2-(2,4-dimethoxy-phenyl)-3H-imidazo[4,5-b]pyridine (0.44 g, 1.7 mmol) in 20 ml of CH 2 Cl 2 , 1,1-dichlorodimethyl ether (0.55 g, 4.8 mmol) was added. The mixture was cooled to 0° C. with a water-ice bath, and 7 ml (7 mmol) of TiCl 4 (1.0 m in CH 2 Cl 2 ) was added dropwise. The mixture was stirred at 0° C. for 2 hrs, then room temperature for overnight. The reaction mixture was poured into ice-water and the precipitate was filtered to give 0.31 g (63%) of 5-(3H-imidazo[4,5-b]pyridin-2-yl)-2,4-dimethoxy-benzaldehyde as a white solid. 1 H-NMR (DMSO-d 6 ) δ 10.22 (s, 1H), 8.67 (s, 1H), 8.56 (d, J=5 Hz, 1H), 8.44 (d, J=8 Hz, 1H), 7.57–7.61 (m, 1H), 6.97 (s, 1H), 4.19 (s, 3H), 4.06 (s, 3H). HMRS (EI) calc. for C 15 H 13 N 3 O 3 : 283.0957; found: 283.0952. The title compound was prepared by condensing 5-(3H-imidazo[4,5-b]pyridin-2-yl)-2,4-dimethoxy-benzaldehyde (Ex-76B) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, mp 222–224° C., 60% yield. 1 H-NMR (DMSO-d 6 ) δ 8.75 (s, 1H), 8.38–8.40 (m, 1H), 8.18 (d, J=9 Hz, 2H), 7.99–8.08 (m, 4H), 7.83 (d, J=15 Hz, 1H), 7.28–7.33 (m, 1H), 6.91 (s, 1H), 4.11 (s, 3H), 4.04 (s, 3H). MS m/z=430 ([M+H] + ). Example 77 2-{4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-2-methyl-propionic acid Ex-77A: To a mixture of aluminum chloride (2.8 g, 20.8 mmol) in carbon disulfide (50 mL) was added acetyl chloride (0.74 mL, 10.4 mmol) followed by addition of 2-methyl-2-phenyl-propionic acid ethyl ester (1.0 g, 5.2 mmol). The reaction mixture was refluxed for 2 hours and then poured into ice containing sulfuric acid (6M). The mixture was partitioned. The aqueous layer was extracted with ethyl acetate. The solution of ethyl acetate was washed with hydrochloric acid (0.5M), saturated solution of sodium bicarbonate and brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography. Elution with ethyl acetate (33%, v/v, in hexane) gave 2-(4-acetyl-phenyl)-2-methyl-propionic acid ethyl ester (0.57 g, 47%). 1 H NMR (CDCl 3 ) δ 7.92 (d, J=7.6 Hz, 2H), 7.42 (d, J=7.6 Hz, 2H), 4.13 (q, J=7.2 Hz, 2H), 2.59 (s, 3H), 1.61 (s, 3H), 1.59 (s, 3H), 1.18 (t, J=7.2 Hz, 3H). The title compound was prepared by condensing 2-(4-acetyl-phenyl)-2-methyl-propionic acid (Ex-77A) and 2,4-dimethoxy-5-thiophen-2-yl-benzaldehyde (Ex-6A) in a similar manner as described in Ex-3. White foam. 1 H-NMR (CCDl 3 ) δ 8.11–7.86 (m, 5H), 7.62–7.46 (m, 3H), 7.42 (d, J=3.2 Hz, 1H), 7.31 (d, J=5.3, 1H), 7.10–7.08 (m, 1H), 6.54 (s, 1H), 3.99 (s, 3H), 3.97 (s, 3H), 1.67 (s, 3H), 1.65 (s, 3H). MS m/z=436 (M + , 55%), 405 ([M−OCH 3 ] + , 100%). Example 78 3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-1-[4-(2H-tetrazol-5-yl)-phenyl]-propenone Ex-78A: A suspension of 4-acetylbenznitrile (2.9 g, 20.0 mmol), sodium azide (1.43 g, 22.0 mmol) and zinc bromide (4.5 g, 20.0 mmol) in water (50 mL) was refluxed for one day. Additional water (40 mL), HCl (3M, 30 mL) and EtOAc (200 mL) were added subsequently. The mixture was stirred until no solid in the aqueous layer. The mixture was then portioned. The aqueous solution was further extracted with EtOAc (3×60 mL). The combined EtOAc was concentrated. The residue was treated with NaOH (0.25 M, 200 mL). After stirred for 50 min, insoluble material was filtered, washed with NaOH (1M). The filtrate was then acidified with HCl (conc.) to pH 3. The resulting white precipitate was filtered, washed with water and dried in vacuo to obtain 1-[4-(2H-tetrazol-5-yl)-phenyl]-ethanone as white solid. 1 H NMR (DMSO-d 6 ) δ 8.17–8.10 (m, 4H), 2.61 (s, 3H). MS m/z=188 (M + ). The title compound was prepared by condensing 1-[4-(2H-tetrazol-5-yl)-phenyl]-ethanone (Ex-78A) and 2,4-dimethoxy-5-thiophen-2-yl-benzaldehyde (Ex-6A) in a similar manner as described in Ex-3. Yellow solid, mp 235° C. (dec.). 1 H-NMR (DMSO-d 6 ) δ 8.33 (d, J=8.4 Hz, 2H), 8.26 (s, 1H), 8.20 (d, J=8.9 Hz, 2H), 8.08 (d, J=16.0 Hz, 1H), 7.93 (d, J=15.0 Hz, 1H), 7.66–7.64 (m, 1H), 7.50–7.48 (m, 1H), 7.12–7.09 (m, 1H), 6.81 (s, 1H), 3.983 (s, 3H), 3.976 (s, 3H). MS m/z=418 (M + , 100%). Example 79 4-[3Z-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid A solution of 4-[3E-(5-benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid (Ex-3, 101.4 mg, 0.23 mmol) in ethyl acetate (889 ml) was stirred in a well lighted-area at room temperature for 36 hours. The solution was concentrated to a yellow solid. The crude material was purified on reversed-phase preparative plates (20×20 cm, RP-18 F 254 , 1 mm) eluted with MEOH/ACN/H 2 O (45:45:10) to give 22.2 mg of the title compound, which was 86% the cis isomer by NMR analysis. 1 H-NMR (DMSO-D 6 , major isomer) δ 7.98 (s, 4H), 7.86 (m, 2H), 7.76 (d, J=9 Hz 1H), 7.56 (s, 1H), 7.28 (m, 2H), 7.17 (d, J=12 Hz, 1H), 6.78 (d, J=12 Hz, 2H), 6.71 (s, 1H), 3.94 (s, 3H), 3.77 (s, 3H). Example 80 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzenesulfonamide To a solution of 4-acetyl-benzsulfonamide (Ex-26A, 0.20 g, 1.0 mmol) and 5-benzo[b]thiophene-2-yl-2,4-dimethoxyphenylbenzaldehyde (Ex-3A, 0.31 g, 1.05 mmol) in DMF (5 mL) and methanol (2 mL) was added lithium methoxide (0.15 g, 4.0 mmol). The reaction mixture was allowed to stir at ambient temperature. The reaction was quenched with water (30 mL) after 2 hours. The aqueous solution was acidified to pH 4 with HCl (3 M) and extracted with ethyl acetate. The combined solution of ethyl acetate was subsequently washed with brine, dried (Na 2 SO 4 ) and concentrated. The solid residue was stirred in ethanol (10 mL) for 1.5 hours, filtered, washed with aqueous ethanol (50%) and dried in vacuo. The title compound was obtained as a yellow solid (0.3 g, 63%), mp 204–205° C. (dec.). 1 H-NMR (DMSO-d 6 ) δ 8.35 (s, 1H), 8.27 (d, J=7.7 Hz, 2H), 8.06 (d, J=16.0 Hz, 1H), 7.97–7.92 (m, 4H), 7.88 (d, J=6.6 Hz, 1H), 7.81 (d, J=7.4 Hz, 1H), 7.53 (s, 2H), 7.37–7.27 (m, 2H), 6.85 (s, 1H), 4.09 (s, 3H), 4.03 (s, 3H). Example 81 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide 4-Acetyl-benzenesulfonamide (Ex-26A) (0.10 g, 0.29 mmol) and 4-acetylbenzenesulfonamide (0.057 g, 0.29 mmol) were dissolved in a dimethylformamide-methanol solution (2.0 mL, 7:3). After complete dissolution, lithium methoxide (0.044 g, 1.2 mmol) was added and the resulting orange slurry was stirred in the dark at room temperature for 4 h. Upon completion, as determined by HPLC, the mixture was diluted with water (15 mL) and extracted with ethyl acetate (3×25 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was taken up in ethanol (2 mL) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. The resulting precipitate was collected on filter paper and dried in vacuo to yield 0.13 g (82%) of the title compound as a yellow solid, mp 186–188° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.23–8.28 (m, 3H), 7.93–8.09 (m, 4H), 7.66 (d, 1H, J=3.0 Hz), 7.56 (brs, 1H), 7.52 (d, 1H, J=5.1 Hz), 7.13 (dd, 1H, J=5.1, 3.0 Hz), 6.89 (s, 1H), 4.34 (t, 2H, J=6 Hz), 4.01 (s, 3H), 3.54–3.58 (m, 4H), 2.38 (t, 2H), J=6 Hz), 2.51–2.53 (m, 4H). MS (ESI) m/z=529 ([M+H] + , 100%). Anal. Calcd. for C 26 H 28 N 2 O 6 S 2 : C, 59.07; H, 5.34; N, 5.30; S, 12.13. Found: C, 58.90; H, 5.3; N, 5.37; S, 12.01. Example 82 2-{5-Methoxy-2-[3-oxo-3-(4-aminosulfonyl-phenyl)-E-propenyl]-4-thiophen-2-yl-phenoxy}-2-methyl-propionic acid The title compound was prepared by condensing 4-acetyl-benzenesulfonamide (Ex-26A) and 2-(2-formyl-5-methoxy-4-thiophen-2-yl-phenoxy)-2-methyl-propionic acid (Ex-59B) in a similar manner as described in Ex-22. Yellow solid, mp 164–165° C., 85% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.21–8.28 (m, 3H), 7.96–8.12 (m, 4H), 7.67 (d, 1H, J=3.0 Hz), 7.56 (brs, 3.0H), 7.14 (dd, 1H, J=5.7, 3.0 Hz), 6.57 (s, 1H), 3.88 (s, 3H), 1.66 (s, 6H). MS (ESI) m/z=502 ([M+H] + , 100%). Anal. Calcd. for C 24 H 23 NO 7 S 2 : C, 57.47; H, 4.62; N, 2.79; S, 12.79. Found: C, 57.70; H, 4.74; N, 2.85; S, 12.51. Example 83 2-{2,4-Dimethoxy-5-[3-oxo-3-(4-aminosulfonyl-phenyl)-E-propenyl]-phenyl}-indole-1-carboxylic acid tert-butyl ester The title compound was prepared by condensing 4-acetyl-benzenesulfonamide (Ex-26A) and 2-(5-formyl-2,4-dimethoxy-phenyl)-indole-1-carboxylic acid tert-butyl ester (Ex-36A) in a similar manner as described in Ex-22. Yellow solid, 40% yield, mp 120–122° C. 1 H-NMR (CDCl 3 ) δ 8.01–8.19 (m, 6H), 7.68 (s, 1H), 7.56 (d, J=8 Hz, 1H), 7.46 (d, J=16 Hz, 1H), 7.21–7.35 (m, 2H), 6.53 (d, J=14 Hz, 2H), 5.01 (s, 2H), 4.00 (s, 3H), 3.85 (s, 3H), 1.42 (s, 9H), MS m/z=563 ([M+H] + ). HRMS (ES+) Calcd. for C 30 H 30 N 2 O 7 S: 563.1852. Found: 563.1862. Example 84 4-{3E-[5-(1H-Indol-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide The title compound was prepared by condensing 4-acetyl-benzenesulfonamide (Ex-26A) and 5-(1H-indol-2-yl)-2,4-dimethoxy-benzaldehyde (Ex-61A) in a similar manner as described in Ex-22. Red solid, 70% yield, mp 185–187° C. 1 H-NMR (DMSO-d 6 ) δ 11.15 (br, s, 1H), 8.33 (s, 1H), 8.24 (d, J=8 Hz, 2H), 8.07 (d, J=15 Hz, 1H), 7.98 (d, J=8 Hz, 2H), 7.80 (d, J=15 Hz, 1H), 7.41–7.55 (m, 4H), 7.03–7.08 (m, 1H), 6.93–6.99 (m, 2H), 6.83 (s, 1H), 4.04 (s, 3H), 3.99 (s, 3H). MS m/z=463 ([M+H] + ). HRMS (ES+) Calcd. for C 25 H 22 N 2 O 5 S: 463.1327. Found: 463.1316. Example 85 4-{3E-[4-Methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide The title compound was prepared by condensing 4-acetyl-benzenesulfonamide (Ex-26A) and 4-methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-benzaldehyde (Ex-66A) in a similar manner as described in Ex-22. Yellow solid, 48% yield, mp 193–196° C. 1 H-NMR (DMSO-d6) δ 8.24 (m, 3H), 8.06 (s, 1H), 7.96 (d, 2H), 7.89 (d, 1H), 7.63 (d, 1H), 7.51 (m, 1H), 7.10 (dd, J=3, 4 Hz, 1H), 6.81 (s, 1H), 4.23 (t, 2H), 3.98 (s, 3H), 3.55 (t, 4H), 2.47 (m, 2H), 2.35 (t, 4H), 1.98 (q, 2H). MS m/z=542 ([M] + , 38%), 100 (100%). Anal. calculated for C 27 H 30 N 2 O 6 S 2 .3/5H 2 O: C, 58.59; H, 5.68; S, 11.59; found C, 58.59,H: 5.55, S, 11.40. Example 86 4-{3E-[2-(3-Hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide 2-(3-Hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-64B) (8.0 g, 24.8 mmol) and 4-acetylbenzenesulfonamide (4.9 g, 24.8 mmol) were dissolved in a dimethylformamide-methanol solution (170 mL, 7:3). After complete dissolution, lithium methoxide (3.8 g, 99.2 mmol) was added and the resulting red-orange slurry was stirred in the dark at room temperature for 3 h. Upon completion, as determined by HPLC, the mixture was diluted with water (500 mL) and extracted with ethyl acetate (6×200 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was taken up in ethanol (150 mL) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. The resulting precipitate was collected on filter paper and dried in vacuo to yield 7.0 g (60%) of the title compound as a light orange solid, mp 123–124° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.25–8.29 (m, 3H), 7.90–8.11 (m, 4H), 7.66 (d, 1H, J=3.0 Hz), 7.56 (brs, 1H), 7.52 (d, 1H, J=5.1 Hz), 7.13 (dd, 1H, J=5.1, 3.0 Hz), 6.88 (s, 1H), 4.67 (t, 2H, J=10.8 Hz), 4.24 (d, 2H, J=6.0 Hz), 4.00 (s, 3H), 3.54–3.65 (m, 4H), 2.09–2.13 (m, 1H). MS (ESI) m/z=504 ([M+H] + , 100%). Anal. Calcd. C 24 H 25 NO 7 S 2 H 2 O: C, 57.24; H, 5.00; N, 2.78; S, 12.73. Found: C, 56.72; H, 5.27; N, 2.71; S, 12.11. Example 87 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-N-isobutyryl-benzenesulfonamide A solution of 4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzenesulfonamide (Ex-80, 0.15 g, 0.31 mmol) in tetrahydrofuran (3 mL) was cooled to −78° C. and a solution of lithium bis(trimethylsilyl)amide (1.0 M in tetrahydrofuran, 0.63 mL, 0.63 mmol) was added dropwise. The solution was allowed to stir at this temperature for 1 hour and warm up to 0° C. Isobutyric acid anhydride (0.31 mL, 1.88 mmol) was added at this temperature. The solution was allowed to stir at 0° C. for 10 min and ambient temperature for 2 hours. The reaction then was quenched with water. The aqueous solution was extracted with ethyl acetate. The combined solution of ethyl acetate was washed with brine, dried over sodium sulfate and concentrated. The residual material was stirred in ethanol for 3 hours, filtered and dried in vacuo to give the title compound as a yellow solid (0.15 g, 87%), mp>240° C. (dec.). 1 H-NMR (CDCl 3 ) δ 8.21 (d, J=8.6 Hz, 2H), 8.13 (d, J=8.7 Hz, 2H), 8.09 (s, 1H), 8.02 (bs, 1H), 7.94 (s, 1H), 7.85–7.78 (m, 2H), 7.68 (s, 1H), 7.55 (d, J=16.9 Hz, 1H), 7.38–7.30 (m, 2H), 6.58 (s, 1H), 4.04 (s, 3H), 4.01 (s, 3H), 2.47–2.38 (m, 1H), 1.14 (d, J=7.1 Hz, 6H). MS m/z=549 (M + , 100%). Example 88 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide, hydrochloride Th 4-{3-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide (Ex-81, 0.065 g, 0.12 mmol) was dissolved in tetrahydrofuran (5 mL) and 3 N HCl (1 mL) was added drop wise to the solution. The resulting yellow slurry was stirred in the dark at room temperature for 30 min. The precipitate was collected and dried in vacuo to yield 0.054 g (78%) of the title compound as a yellow solid, mp 235° C. (dec). 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.31–8.34 (m, 3H), 8.13 (d, 1H, J=15.0 Hz), 7.92–8.01 (m, 3H), 7.70 (d, 1H, J=4.0 Hz), 7.54 (m, 3H), 7.15–7.17 (m, 1H), 6.92 (s, 1H), 4.64 (brs, 2H), 4.03 (s, 5H), 3.72–3.79 (m, 4H), 3.56–3.60 (m, 4H). MS (ESI) m/z=529 ([M+H] + , 100%). Anal. Calcd. for C 26 H 29 ClN 2 O 6 S 2 : C, 55.26; H, 5.17; Cl, 6.27; N, 4.96; S, 11.35. Found: C, 55.31; H, 5.17; Cl, 6.32; N, 4.98; S, 11.20. Example 89 4-{3E-[4-Methoxy-2-(1H-tetrazol-5-ylmethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide Ex-89A: (2-Acetyl-5-methoxy-4-thiophen-2-yl-phenoxy)-acetonitrile was prepared in an analogous fashion as described in Ex-29C using iodoacetonitrile. The crude solid was slurried in ethyl acetate (50 mL) to remove residual impurities. The resulting solid was collected on filter paper and dried in vacuo to give the expected product as an orange solid (70%), mp 175–176° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.29 (s, 1H), 8.17 (s, 1H), 7.48 (d, 1H, J=3.6 Hz), 7.35 (d, 1H, J=5.1 Hz), 7.10 (dd, 1H, J=5.1, 3.6 Hz), 6.64 (s, 1H), 4.96 (s, 2H), 4.06 (s, 3H). MS (EI) m/z=273 ([M] + , 99%), 233 (100%). Anal. Calcd. for C 14 H 11 NO 3 S: C, 61.52; H, 4.06; N, 5.12; S, 11.73. Found: C, 61.65; H, 4.20; N, 5.16; S, 11.59. Ex-89B: (2-Acetyl-5-methoxy-4-thiophen-2-yl-phenoxy)-acetonitrile (Ex-89A, 0.30 g, 1.1 mmol) was slurried in a mixture of water:isopropanol (3 mL, 2:1) to obtain a well-dispersed solution. Sodium azide (0.079 g, 1.2 mmol) followed by zinc bromide (0.25 g, 1.1 mmol) were added and the reaction was heated to reflux and vigorously stirred for 24 h. Additional solvent (1 mL, 1:1 water:isopropanol) was added after 10 h at reflux due to evaporation. The reaction was diluted with an ethyl acetate:tetrahydrofuran mixture (25 mL, 2:1) and a 3 N HCl solution (10 mL) and vigorously stirred until a homogenous solution was obtained (1 h). The layers were separated and the aqueous was extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried over sodium sulfate and concentrated to a dark green solid. Silica gel chromatography (15% methanol/methylene chloride containing 1% acetic acid) gave 0.22 g (65%) of 4-methoxy-2-(1H-tetrazol-5-ylmethoxy)-5-thiophen-2-yl-benzaldehyde as a pale green solid. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.33 (s, 1H), 7.97 (s, 1H), 7.52–7.56 (m, 2H), 7.10–7.12 (m, 2H), 5.81 (s, 2H), 4.05 (s, 3H). MS (ESI) m/z=317 ([M+H] + , 100%), HRMS (ESI) Calcd. for C 27 H 25 NO 7 S: 317.0708. Found: 317.0712. The title compound was prepared by condensing 4-acetyl-benzenesulfonamide (Ex-26A) and 4-methoxy-2-(1H-tetrazol-5-ylmethoxy)-5-thiophen-2-yl-benzaldehyde (Ex-89A) in a similar manner as described in Ex-22. Yellow solid, mp 163–164° C. (dec), 60% yield. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.31–8.34 (m, 3H), 7.92–8.15 (m, 4H), 7.70 (d, 1H, J=4.0 Hz), 7.54 (m, 3H), 7.15–7.17 (m, 1H), 6.92 (s, 1H), 4.64 (brs, 2H), 4.03 (s, 5H). MS (ESI) m/z=498 ([M+H] + , 100%). Anal. Calcd. for C 22 H 19 N 5 O 5 S 2 .1½H 2 O: C, 50.37; H, 4.23; N, 13.35; S, 12.23. Found: C, 50.48; H, 4.24; N, 12.95; S, 12.35. Example 90 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-N-(2-morpholin-4-yl-ethyl)-benzamide To a solution of 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid (Ex-3, 0.44 mg, 1 mmol) and 2-morpholin-4-yl-ethylamine (0.18 mL) in dichloromethane (20 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.38 g, 2 mmol) and the mixture was stirred at room temperature for four hours. It was poured into brine (100 mL) and extracted with dichloromethane (2×50 mL). The organic phase was dried and evaporated. Chromatography (dichloromethane/methanol 50:1) gave the title compound as a yellow solid (0.43 g, 77%). 1 H-NMR (300 MHz, CDCl 3 ) δ 8.12 (d, J=16 Hz, 1H), 8.09 (d, J=8 Hz, 2H), 7.95 (s, 1H), 7.90 (d, J=8 Hz, 2H), 7.77–7.85 (m, 2H), 7.68 (s, 1H), 7.56 (d, J=16 Hz, 1H), 7.29–7.40 (m, 2H), 6.80–6.85 (br s, 1H), 6.58 (s, 1H), 4.04 (s, 3H), 4.01 (s, 3H), 3.75 (t, J=5 Hz, 4H), 3.59 (quad, J=5 Hz, 2H), 2.64 (t, J=5 Hz, 2H), 2.53 (t, J=5 Hz, 4H). Anal. calc. for C 32 H 32 N 2 O 5 S.H 2 O: C, 67.94; H, 5.88; N, 4.95; found: C, 68.12; H, 5.92; N, 4.96. Example 91 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-N-(2,2,2-trifluoro-ethyl)-benzamide The title compound was prepared in a similar manner as described in Ex-90. Yellow solid, 53% yield, mp 215–217° C. 1 H-NMR (Aceton-d 6 ) δ 8.46 (br, s, H), 8.12–8.24 (m, 4H), 8.06 (d, J=8 Hz, 2H), 7.78–7.91 (m, 4H), 7.28–7.36 (m, 2H), 6.92 (s, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 2.79 (s, 2H). MS m/z=526 ([M+H] + ). HRMS (ES+) Calcd. for C 28 H 22 F 3 NO 4 S: 526.1300. Found: 526.1324. Example 92 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzamide Ex-92A: To a solution of 4-acetyl-benzoic acid (0.5 g, 3.05 mmol) in tetrahydrofuran (10 mL) was added carbonyldiimidazole (0.74 g, 4.75 mmol). The solution was allowed to stir at ambient temperature for one hour and cooled to 0° C. followed by addition of ammonia (28% in water, 3 mL, 21 mmol). The solution was continued to stir at 0° C. for another one hour. The solvent was removed under reduced pressure. The residue was treated with water, filtered, washed with water, dried in vacuo to give 4-acetyl-benzamide (0.25 g, 50%) as a white solid. 1 H NMR (DMSO-d 6 ) δ 8.11 (bs, 1H), 8.00 (d, J=9 Hz, 2H), 7.95 (d, J=9 Hz, 2H), 7.53 (bs, 1H), 2.59 (s, 3H). To a solution of 4-acetyl-benzamide (Ex-92A, 0.25 g, 1.53 mmol) and 2-(2-morpholin-4-yl-ethoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-60A, 0.53 g, 1.53 mmol) in DMF (7 mL) and methanol (3 mL) was added lithium methoxide. The solution was allowed to stir at ambient temperature. The reaction was quenched with water after 2 hours. The aqueous solution was extracted with ethyl acetate. The combined extract was washed with NaHCO 3 , NH 4 Cl, brine, dried (Na 2 SO 4 ) and concentrated. The residue was stirred in ethanol overnight to afford the title compound as a yellow solid (0.43 g, 57%), mp 183–184° C. 1 H-NMR (CDCl 3 ) δ 8.09–8.04 (m, 3H), 7.93 (d, J=8.3 Hz, 2H), 7.87 (s, 1H), 7.57 (d, J=15.7 Hz, 1H), 7.42 (d, J=3.9 Hz, 1H), 7.32 (d, 4.4 Hz, 1H), 7.11–7.08 (m, 1H), 6.55 (s, 1H), 6.25 (bs, 1H), 5.75 (bs, 1H), 4.25 (t, J=5.9 Hz, 2H), 3.98 (s, 3H), 3.71 (t, J=4.2 Hz, 4H), 2.92 (t, J=5.7 Hz, 2H), 2.59 (t, J=4.6 Hz, 4H). MS m/z=493 ([M+H] + , 100%). Example 93 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamide To a solution of 4-acetyl-benzamide (0.3 g, 1.84 mmol) and 5-(benzo[b]thein-2yl)-2,4-dimethoxybenzaldehyde (0.55 g, 1.84 mmol) in a mixture of N,N-dimethylformamide (7 mL) and methanol (3 mL) was added lithium methoxide (0.14 g, 3.68 mmol). The reaction mixture was allowed to stir at ambient temperature for 9 hours. The resulting precipitate was collected by filtration, washed with methanol, dried in vacuo to obtain the title compound as a yellow solid (5.56 g, 68%). Alternatively, to mixture of 4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid (Ex-3, 3.0 g, 6.75 mmol), 1-(3-dimethylaminopropyl)3-ethylcarbodiimide hydrochloride (1.81 g, 9.45 mmol), 1-hydroxybenzotriazole hydrate (1.09 g, 8.10 mmol) and ammonium chloride (1.81 g, 33.7 mmol) in N,N-dimethylformamide (60 mL) was added triethylamine (2.4 mL, 16.9 mmol). The reaction mixture was allowed to stir overnight at ambient temperature. Any insoluble material was removed by filtration. The filtrate was diluted with ethyl acetate to 180 mL. The solution of ethyl acetate was washed with a saturated solution of sodium bicarbonate, brine, dried over sodium sulfate and concentrated to give the title compound as a yellow solid (2.82 g, 94%), mp 240–241° C. 1 H-NMR (DMSO-d 6 ) δ 8.37 (s, 1H), 8.19 (d, J=7.8 Hz, 2H), 8.12 (d, J=15.3 Hz, 1H), 8.04–7.91 (m, 6H), 7.83 (d, J=7.5 Hz, 1H), 7.55 (s, 1H), 7.36–7.30 (m, 2H), 6.87 (s, 1H), 4.04 (s, 3H), 4.01 (s, 3H). MS m/z=444 ([M+H] + , 100%). Example 94 4-{3E-[4-Methoxy-2-(3-morpholin4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzamide The title compound was prepared by condensing 4-Acetyl-benzamide (Ex-92A) and 4-methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-benzaldehyde (Ex-66A) in a similar manner as described in Ex-92. Orange solid, mp 81–83° C. 1 H-NMR (CDCl 3 ) δ 8.08 (m, 3H), 7.94 (d, 2H), 7.86 (s, 1H), 7.56 (d, 1H), 7.41 (d, 1H), 7.32 (d, 1H), 7.10 (m, 1H), 6.55 (s, 1H), 4.19 (t, 2H), 3.99 (s, 3H), 3.72 (t, 4H), 2.59 (t, 2H), 2.12 (t, 4H), 1.98 (quintet, 2H). MS m/z=506 ([M] + , 34%), 100 (100%). 28%. Anal. calculated for C 28 H 30 N 2 O 5 S.2/5H 2 O: C, 65.45; H, 6.04; S, 6.24; found C, 65.30; H, 6.16; S, 6.17. Example 95 N-Acetyl-4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamide A suspension of 4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamide (Ex-93, 0.5 g, 1.13 mmol) in THF (15 mL) was cooled to −78° C. followed by addition of lithium bis(trimethylsilyl)amide (1.0 M in THF, 2.3 mL, 2.3 mmol). The mixture was stirred at this temperature for 1 hour and warmed up to 0° C. Acetic anhydride (0.48 mL, 6.8 mmol) was then added dropwise. After the addition was complete the reaction mixture was warmed up to ambient temperature and stirred for 2 hours. The reaction was quenched with water. The aqueous solution was extracted with ethyl acetate. The combined extract was washed with NH 4 Cl, brine, dried and concentrated. The residue was purified by flash chromatography. Elution with 50% EtOAc/hexane gave the title compound as yellow solid (0.16 g, 29%), mp 228–229° C. 1 H-NMR (CCDl 3 ) δ 8.52 (s, 1H), 8.15–8.10 (m, 3H), 7.96 (d, J=7.6 Hz, 2H), 7.85–7.77 (m, 2H), 7.67 (s, 1H), 7.55 (d, J=16.7 Hz, 1H), 7.34–7.29 (m, 3H), 6.58 (s, 1H), 4.05 (s, 3H), 4.01 (s, 3H), 2.65 (s, 3H). MS m/z=485 (M + , 100%). Example 96 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-N-isobutyryl-benzamide The title compound was prepared in a similar manner as described in Ex-95 from -[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamide (Ex-93) and isobutyric anhydride. Yellow solid, mp 208–209° C. 1 H-NMR (CCDl 3 ) δ 8.14 (s, 1H), 8.15–8.10 (m, 3H), 7.96 (d, J=7.2 Hz, 2H), 7.85–7.77 (m, 2H), 7.67 (s, 1H), 7.56 (d, J=16.2 Hz, 1H), 7.38–7.29 (m, 3H), 6.59 (s, 1H), 4.05 (s, 3H), 4.01 (s, 3H), 3.68–3.59 (m, 1H), 1.28 (d, J=6.2 Hz, 6H). MS m/z=513 (M + , 93%), 425 (100%). Example 97 4(3E-{4-[3-(4-Thiophen-2-yl-phenyl)-acryloyl]-phenyl}-ureido)-acetic acid A solution of (3-{4-[3-(4-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-ureido)-acetic acid ethyl ester (Ex-15, 151.3 mg, 0.35 mmol) in THF:MeOH:H 2 O (2:1:1, 6 mL) was treated with lithium monohydrate (73.2 mg, 1.74 mmol) and stirred for 4 hours. The reaction mixture was titrated with 5N HCl to a pH2. The mixture was extracted with ethyl acetate (30 mL). The organic phase was collected, dried over Na 2 SO 4 , and concentrated to a pure yellow solid (131.7 mg, 93%), mp 222–225° C. 1 H-NMR (DMSO-d6) δ 9.27 (br s, 1H), 8.14 (d, 2H), 7.87 (m, 3H), 7.71 (d, 3H), 7.56 (m, 4H), 7.14 (t, 1H), 6.54 (t, 1H), 3.78 (d, 2H). MS m/z=407 ([M+H] + , 88%), 306 (100%). Anal. calculated for C 22 H 18 N 2 O 4 S.1/2H 2 O: C, 63.60; H, 4.61; S, 7.72; found C, 63.23; H, 4.70; S: 7.66. Example 98 N-{4-[3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-N-methyl-methanesulfonamide A solution of N-{4-[3E-(3,4-dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-methanesulfonamide (Ex-14, 90 mg, 0.20 mmol) in anhydrous DMF was treated with potassium carbonate (56.1 mg, 0.41). Methyl iodide (126.32 uL, 2.03 mmol) was added to the reaction mixture which was then refluxed for 1.5 hours under inert conditions. The reaction was diluted with water (25 mL) and extracted with diethyl ether (2×50 mL). The organic portion was dried over sodium sulfate, filtered, and concentrated to a yellow oil. The crude material was purified by silica gel chromatography (30–50% ethyl acetate/hexanes) to give 42 mg (45%) of the title compound as a yellow solid. 1 H-NMR (CDCl 3 ) δ 8.06 (d, 2H), 7.59 (d, 1H), 7.54 (m, 4H), 7.42 (m, 2H), 7.12 (m, 2H), 3.97 (s, 3H), 3.88 (s, 3H), 3.40 (s, 3H), 2.89 (s, 3H). MS m/z=457 ([M] + , 100%). Example 99 3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-1-[4-(D-glucopyranosylamino)-phenyl]-propenone Ex-99A: D-Glucose (1.8 g, 10 mmol) and 4-aminoacetophenone (1.35 g, 10 mmol) were mixed in ethanol (50 ml), acetic acid (5 drops) was added, and the mixture was stirred at reflux for 2 hours. Water (2 ml) was added and the mixture became a homogeneous solution and was then stirred at reflux for 4 hours. Upon cooling to room temperature the precipitate was filtered out, rinsed with ethanol, and dried to give 4-(D-glucopyranosylamino)acetophenone as a white solid (1.21 g, 41%), mp 209–210° C. (dec). 1 H-NMR (DMSO-D 6 ) δ 7.71 (d, J=8 Hz, 2H), 7.06 (d, J=8 Hz, 1H), 6.69 (d, J=8 Hz, 2H), 4.98 (d, J=4 Hz, 1H), 4.89 (d, J=7 Hz), 4.38–4.45 (m, 2H), 3.55–3.64 (m, 1H), 3.30–3.46 (m, 1H), 3.00–3.30 (m, 4H), 2.38 (s, 3H). MS m/z=297 ([M] + , 15%), 148 (100%). 4-(D-Glucopyranosylamino)acetophenone (Ex-99A, 326 mg, 0.6 mmol) and (benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde (Ex-3A, 150 mg, 0.5 mmol) were mixed in DMF (10 ml) and methanol (5 ml). Lithium methoxide (120 mg) was added, and the mixture was stirred at room temperature for 18 hours. Lithium methoxide (120 mg) was added again and the mixture was stirred overnight. Saturated sodium chloride solution (50 ml) was added and the mixture was extracted with dichloromethane. Chromatography (dichloromethane/methanol 10:1) gave an oily yellow residue as the title compound (20 mg, 6%). 1 H-NMR (DMSO-D 6 ) δ 8.29 (s, 1H), 7.78–8.02 (m, 7H), 7.25–7.38 (m, 2H), 7.15 (d, 1H), 6.84 (s, 1H), 6.77 (d, 2H), 4.99 (d, 1H), 4.86–4.95 (m, 2H), 4.41–4.49 (m, 2H), 4.02 (s, 3H), 3.98 (s, 3H), 3.00–3.45 (m, 6H). MS m/z=578 ([M+H] + , 100%). Example 100 2-{4-[3-(4-Methanesulfonylamino-phenyl)-3-oxo-E-propenyl]-5-methoxy-2-thiophen-2-yl-phenoxy}-2-methyl-propionic acid Ex-100A: A solution of 4-aminoacetophenone (5.0 g, 37.0 mmol) and pyridine (3.0 mL) in anhydrous dichloromethane (300 mL) was treated with mesyl chloride (2.86 mL, 37.0 mmol). The reaction was stirred for 84 hours at room temperature under nitrogen, and then quenched with saturated NH 4 Cl solution (100 mL). The organic phase was collected, washed with water (100 mL) and brine, dried over sodium sulfate, and concentrated over silica. The material was purified by silica gel chromatography (50% ethyl acetate/hexanes) to give 4.72 g (60%) of N-(4-acetyl-phenyl)-methanesulfonamide as a yellowish oil. 1 H-NMR (DMSO-d6) δ 10.28 (s, 1H), 7.90 (d, 1H), 7.24 (d, 1H), 3.06 (s, 3H), 2.48 (s, 3H). A solution of N-(4-acetyl-phenyl)-methanesulfonamide (Ex-100A, 279.6 mg, 1.31 mmol) and 2-(4-formyl-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid (Ex-47D, 400 mg, 1.20 mmol) in DMF (5.25 mL) and MeOH (2.25 mL) was treated with lithium methoxide (182.2 mg, 4.8 mmol) and stirred for 5 hours at room temp. under nitrogen atmosphere. The reaction mixture was diluted with water (25 mL) which was then extracted with isopropyl acetate (2×50 mL). The aqueous portion was collected and acidified to a pH of 3 with 3N HCl. The aqueous solution was then extracted with isopropyl acetate (2×50 mL). The organic was collected, dried over sodium sulfate, and concentrated to a green solid. Attempted to recrystallize crude material from ethanol/hexanes; however, this mixture was concentrated and stirred with ethyl acetate (3 mL) to give 95.6 mg (14%) of the title compound as a yellow solid, mp 181–183° C. 1 H-NMR (DMSO-d6) δ 10.31 (br s, 1H), 8.24 (s, 1H), 8.12 (d, 2H), 7.95 (d, 1H), 7.87 (d, 1H), 7.67 (d, 1H), 7.50 (d, 1H), 7.30 (d, 2H), 7.09 (t, 1H), 6.45 (s, 1H), 3.81 (s, 3H), 3.08 (s, 3H), 1.65 (s, 6H). MS m/z=516 ([M+H] + , 100%). HRMS m/z: calc. 516.1150, found 516.1165. Example 101 2-(4-{3-[4-(Methanesulfonyl-methyl-amino)-phenyl]-3-oxo-E-propenyl}-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid Ex-101A: A solution of N-(4-acetyl-phenyl)-methanesulfonamide (Ex-100A, 2.0 g, 9.4 mmol) in anhydrous DMF (300 mL) was treated with potassium carbonate (2.59 g, 18.8 mmol), followed by the addition of methyl iodide (5.85 mL, 94 mmol). The reaction mixture refluxed for two hours and was then treated with more methyl iodide (5.85 mL, 94 mmol). The reaction refluxed for another two hours, and reaction completeness was confirmed by HPLC analysis. The reaction was quenched with water (100 mL) and extracted with ethyl acetate (2×100 mL). The organic phase was collected, dried over sodium sulfate, and concentrated to a clear oil with residual DMF. Water (25 mL) was added to precipitate a white solid. The white solid was then filtered and dried by vacuum oven at 20° C. (−20 mm Hg) to give 1.37 g (64%) of N-(4-acetyl-phenyl)-N-methyl-methanesulfonamide. 1 H-NMR (CDCl 3 ) δ 7.88 (d, 2H), 7.48 (d, 2H), 3.38 (s, 3H), 2.86 (s, 3H), 2.60 (s, 3H). HRMS m/z: calc. 530.1307, found 530.1313. A solution of N-(4-acetyl-phenyl)-N-methyl-methanesulfonamide (Ex-101A, 298 mg, 1.31 mmol) and 2-(4-formyl-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid (Ex-47D, 400 mg, 1.20 mmol) in DMF (5.25 mL) and MeOH (2.25 mL) was treated with lithium methoxide (182 mg, 4.8 mmol) and stirred for 6 hours at room temperature under nitrogen atmosphere. The reaction mixture was diluted with water (25 mL) which was then extracted with isopropyl acetate (2×50 mL). The aqueous portion was collected and acidified to a pH of 3 with 3N HCl. The aqueous solution was then extracted with isopropyl acetate (2×50 mL). The organic was collected, dried over sodium sulfate, and concentrated to a yellow foam. The crude material was purified by silica gel chromatography (50% ethyl acetate/hexanes; 10% MeOH/CH 2 CL 2 ) to give 293 mg (42%) of the title compound as a yellow solid, mp 197–200° C. 1 H-NMR (DMSO-d6) δ 8.20 (s, 1H), 8.12 (d, 2H), 8.00 (d, 1H), 7.83 (d, 1H), 7.66 (dd, J=2, 2 Hz, 1H), 7.53 (d, 2H), 7.44 (d, 1H), 7.06 (dd, J=2, 4 Hz, 1H), 6.78 (s, 1H), 3.82 (s, 3H), 3.28 (s, 3H), 2.98 (s, 3H), 1.56 (s, 3H). MS m/z=530 ([M+H] + , 100%). Example 102 3-Amino-4-{4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-phenylamino}-cyclobut-3-ene-1,2-dione Ex-102A: To a solution of 2.7 g (20 mmol) of 4′-aminoacetophenone in 90 mL of ethanol, 4.5 g (20 mmol) of 3,4-dibutoxy-3-cyclobutene-1,2-dione (Aldrich) was added. The mixture was then heated to reflux overnight. A light yellow precipitate formed. To the reaction mixture, 20 mL (40 mmol) of ammonia (2.0 M in ethanol) was added, and the resultant mixture was stirred at room temperature for 2 hr. The light yellow solid was filtered and washed with ethanol to give 2.4 g (52%) of 3-(4-acetyl-phenylamino)-4-amino-cyclobut-3-ene-1,2-dione. 1 H-NMR (DMSO-d 6 ) δ 9.99 (br, 1H), 7.90 (d, J=8 Hz, 2H), 7.50 (d, J=8 Hz, 2H), 4.31 (br, 2H), 2.48 (s, 3H). HMRS (EI) calcd. for C 12 H 10 N 2 O 3 : 230.0691; found: 230.0691. 3-(4-Acetyl-phenylamino)-4-amino-cyclobut-3-ene-1,2-dione (Ex-102A, 0.46 g, 2 mmol), and 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde (Ex-3A, 0.596 g, 2 mmol) were dissolved in DMF (10 mL) under nitrogen, and 4.0 ml (4 mmol) of LiOMe (1.0 M in MeOH) was added. The mixture was stirred under nitrogen at room temperature over night. The reaction mixture was poured into ice-water, acidified to pH1 with 3N HCl, extracted with dichloromethane. The combined organic phase was then washed with brine and water, dried over MgSO 4 , column chromatography (5% MeOH in CH 2 Cl 2 ) to give 57 mg (5.4%) title compound as a yellow solid, mp>260° C. 1 H-NMR (DMSO-d 6 ) δ 10.08 (s, 1H), 8.36 (s, 1H), 8.18 (d, J=8 Hz, 2H), 8.03 (d, J=15 Hz, 1H), 7.82–7.95 (m, 4H), 7.57 (d, J=8 Hz, 2H), 7.27–7.37 (m, 2H), 6.85 (s, 1H), 4.02 (s, 3H), 3.99 (s, 3H), 3.26 (s, 2H). MS m/z=511[M+H] + , (20%), 416 (100%). HRMS (ES+) Calcd. for C 29 H 22 N 2 O 5 S: 511.1327. Found: 511.1326. Example 103 5-[3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzo[1,3]dioxole-2,2-dicarboxylic acid, diethyl ester Ex-103A: To a solution of KOH (1.25 M, 200 mL) were added 3,4-dihydroxy-acetophenone (2.0 g, 13.1 mmol) and cetyltrimethylamonium chloride (25% in water, 17 mL, 13.1 mmol). The suspension was stirred at ambient temperature for 10 min followed by the addition of a suspension of 3,4-dimethoxy-5-thiophen-2yl-benzaldehyde (Ex-6A, 3.9 g, 15.8 mmol) in ethanol (10 mL). The reaction mixture was allowed to stir at ambient temperature overnight and was acidified with concentrated HCl to pH 3, saturated with NaCl, extracted with CH 2 Cl 2 . The combined solution of CH 2 Cl 2 was washed with brine, dried (Na 2 SO 4 ) and concentrated under reduced pressure. The crude product was purified by flash chromatography. Elution with 50% EtOAc/hexane gave 1-(3,4-dihydroxy-phenyl)-3E-(3,4-dimethoxy-5-thiophen-2-yl-phenyl)-propenone as a yellow oil. 1 H NMR (DMSO-d 6 ) δ 7.88 (s, 1H), 7.83–7.81 (m, 2H), 7.76 (d, J=2.4 Hz, 1H), 7.68–7.74 (m, 2H), 7.61–7.57 (m, 1H), 7.51 (s, 1H), 7.50 (d, J=5.2 Hz, 1H), 7.13 (t, J=4.5 Hz, 1H), 6.85 (d, J=8.7 Hz, 1H), 3.92 (s, 3H), 3.77 (s, 3H). MS m/z=382 (M + , 100%). 1-(3,4-Dihydroxy-phenyl)-3E-(3,4-dimethoxy-5-thiophen-2-yl-phenyl)-propenone (106 mg), diethyl dibromomalonate (380 mg) and potassium carbonate (500 mg) was mixed in acetone (15 ml) and the mixture was stirred at room temperature over a weekend. It was poured into ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was dried and evaporated. Chromatography (hexanes/ethyl acetate 4:1) gave an oily residue. Crystallization from hexanes and dichloromethane gave the title compound as a slightly yellow solid (70 mg), mp 125–126° C. 1 H-NMR (DMSO-d6) δ 7.76 (d, J=15 Hz, 1H), 7.73 (dd, J=2, 7 Hz, 1H), 7.64 (d, J=2 Hz, 1H), 7.54 (d, J=1 Hz, 1H), 7.53 (d, J=2 Hz, 1H), 7.39 (d, J=5 Hz, 1H), 7.38 (d, J=15 Hz, 1H), 7.11 (dd, J=2, 5 Hz, 1H), 7.08 (d, J=1 Hz, 1H), 7.05 (d, J=7 Hz, 1H), 3.97 (s, 3H), 3.87 (s, 3H), 4.41 (quad, J=7 Hz, 4H), 1.30 (t, J=7 Hz, 6H). Example 104 4-[3E-(2,4-Dimethoxy-5-pyridin-3-yl-phenyl)-acryloyl]-benzenesulfonamide Ex-104A: 2,4-Dimethoxy-5-pyridin-3-yl-benzaldehyde was prepared in a similar manner as described in Ex-3A from pyridine-3-boronic acid and 5-bromo-2,4-dimethoxybenzaldehyde, 68% yield. 1 H-NMR (CDCl 3 ) δ 10.33 (s, 1H), 8.71 (d, J=1 Hz, 1H), 8.51–8.53 (m, 1H), 7.81 (s, 1H), 7.74–7.78 (m, 1H), 7.27–7.31 (m, 1H), 6.52 (s, 1H), 3.99 (s, 3H), 3.91 (s, 3H). HMRS (EI) calcd. for C 14 H 13 NO 3 : 243.0895; found: 243.0888. The title compound was prepared by condensing 2,4-dimethoxy-5-pyridin-3-yl-benzaldehyde (Ex-104A) and 4-acetyl-benzenesulfonamide (Ex-26A) in a similar manner as described in Ex-22. Yellow solid, 51% yield, mp 253–255° C. 1 H-NMR (DMSO-d6) δ 8.69 (d, J=1 Hz, 1H), 8.50 (d, J=4 Hz, 1H), 8.25 (d, J=9 Hz, 2H), 8.08 (d, J=15 Hz, 1H), 8.02 (s, 1H), 7.84–7.94 (m, 4H), 7.51 (s, 2H), 7.40–7.44 (m, 1H), 6.82 (s, 1H), 3.98 (s, 3H), 3.88 (s, 3H). MS m/z=424([M] + , 45%), 393 (100%). HMRS (EI) calcd. for C 22 H 20 N 2 O 5 S: 424.1093; found 424.1100. Example 105 4-{3E-[5-(2-Cyclopropyl-1H-imidazol-4-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid, hydrochloride Ex-105A: A solution of 2-bromo-1-(3,4-dimethoxy-phenyl)-ethanone (0.3 g, 1.16 mmol), cyclopropanecarboxamidine (0.14 g, 1.16 mmol) and sodium hydroxide (0.18 g, 4.5 mmol) in ethanol was refluxed overnight. The solvent was removed under reduced pressure, the residue taken up to water. The aqueous solution was then extracted with dichloromethane which was subsequently washed with brine, dried over sodium bicarbonate and concentrated. The crude product was purified by flash chromatography. Elution with ethyl acetate (50%, v/v, in hexane) then methanol (10%, v/v in dichloromethane) afforded 2-cyclopropyl-4-(2,4-dimethoxy-phenyl)-1H-imidazole as white solid (0.1 5 g, 53%): 1 HNMR (CDCl 3 ) δ 9.50 (bs, 1H), 7.63 (s, 1H), 7.20 (s, 1H), 6.57–6.53 (m, 2H), 3.93 (s, 3H), 3.03 (s, 3H), 1.97–1.93 (m, 1H), 1.00–0.94 (m, 4H). MS m/z=245 ([M+H] + , 100%). Ex-105B: To a solution of 2-cyclopropyl-4-(2,4-dimethoxy-phenyl)-1H-imidazole (0.51 g, 2.09 mmol) was added dichloromethyl methyl ether (0.28 mL, 3.13 mmol) followed by addition of titanium tetrachloride (1.0M in dichloromethane, 8.4 mL, 8.4 mmol) dropwise at 0° C. The solution was allowed to warm up to ambient temperature and stir for 4.5 hours. The reaction mixture was then poured into ice. The aqueous layer was adjusted to pH 12 and extracted with dichloromethane. The combined solution of dichloromethane was washed with saturated solution of sodium bicarbonate, brine, dried over sodium sulfate and concentrated to afford 5-(2-cyclopropyl-1H-imidazol-4-yl)-2,4-dimethoxy-benzaldehyde which was used without further purification. 1 H NMR (DMSO-d 6 ) δ 13.95 (bs, 1H), 10.22 (s, 1H), 8.09 (s, 1H), 7.70 (s, 1H), 6.88 (s, 1H), 4.04 (s, 3H), 4.00 (s, 3H), 2.25 (m, 1H), 1.20 (m, 4H). MS m/z=245 ([M+H] + , 100%). The title compound was prepared by condensing 5-(2-cyclopropyl-1H-imidazol-4-yl)-2,4-dimethoxy-benzaldehyde (Ex-105B) and 4-acetylbenzoic acid in a similar manner as described in Ex-3. Yellow solid, m.p.>240° C. 1 H NMR (DMSO-d 6 ) δ 13.31 (bs, 1H), 8.29 (d, J=8.9 Hz, 2H), 8.06–8.01 (m, 3H), 7.91 (s, 1H), 7.67 (s, 1H), 6.83 (s, 1H), 4.02 (s, 3H), 3.98 (s, 3H), 1.29–1.22 (m, 4H). MS m/z=419 ([M+H] + , 100%). Example 106 4-{3E-[4-(3-Hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide The title compound was prepared by condensing 4-(3-hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-50C) and 4-acetyl-benzenesulfonamide (Ex-26A) in a similar manner as described in Ex-22. Yellow solid, 72% yield, mp 191–192° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.29–8.32 (m, 3H), 8.09 (d, 1H, J=16.0 Hz), 7.99 (d, 2H, J=8.1 Hz), 7.92 (d, 1H, J=16.0 Hz), 7.70 (d, 1H, J=3.3 Hz), 7.53–7.56 (m, 3H), 7.14 (dd, 1H, J=5.4, 3.3 Hz), 6.87 (s, 1H), 4.61 (t, 2H, J=5.1 Hz), 4.28 (d, 2H, J=5.1 Hz), 4.00 (s, 3H), 3.60–3.67 (m, 4H), 2.11–2.15 (m, 1H). MS (ESI) m/z=504 ([M+H] + , 100%). Anal. Calcd. for C 24 H 25 NO 7 S 2 .½H 2 O: C, 56.23; H, 5.11; N, 2.73; S, 12.51. Found: C, 56.32; H, 5.06; N, 2.83; S, 12.55. Example 107 1-(4-Benzenesulfonyl-phenyl)-3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-propenone The title compound was prepared by condensing 1-(4-benzenesulfonyl-phenyl)-ethanone with 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde (Ex-3A) in a similar manner as described in Ex-3, 5% yield. The product was purified using column chromatography. Yellow solid, mp 127–128° C. 1 H-NMR (CDCl 3 ) δ 8.05–8.11 (m, 5H), 7.97 (d, J=7 Hz, 2H), 7.91 (s, 1H), 7.76–7.84 (m, 2H), 7.66 (s, 1H), 7.46–7.60 (m, 4H), 7.26–7.37 (m, 2H), 6.56 (s, 1H), 4.03 (s, 3H), 3.99 (s, 3H). MS m/z=540 ([M] + , 100%). HRMS (EI) Calcd. for C 13 H 24 O 5 S 2 : 540.1605. Found: 540.1074. Example 108 1-(4-Acetyl-phenyl)-3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-propenone The title compound was prepared by condensing 1-(4-acetyl-phenyl)-ethanone with 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde (Ex-3A) in a similar manner as described in Ex-3. The product was purified using column chromatography. Yellow solid, 2% yield, mp 165–167° C. 1 H-NMR (CDCl 3 ) δ 8.06–8.12 (m, 5H), 7.92 (s, 1H), 7.75–7.82 (m, 2H), 7.65 (s, 1H), 7.55 (d, J=15 Hz, 1H), 7.28–7.33 (m, 2H), 6.56 (s, 1H), 4.01 (s, 3H), 3.98 (s, 3H). MS m/z=442 ([M] + , 100%). HMRS (EI) calcd. for C 27 H 22 O 4 S: 442.1239; found: 442.1229. Example 109 4-{3E-[5-(4-Isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide Ex-109A: A solution of 2,4-dimethoxy-benzoic acid methyl ester (4.24 g, 21.6 mmol) and hydrazine (3.4 mL, 108.1 mmol) in methanol (50 mL) was refluxed overnight. Solvent was removed under reduced pressure. The residue was re-dissolved in ethyl acetate. The solution of ethyl acetate was washed with saturated solution of sodium bicarbonate and brine, dried over sodium carbonate and concentrated to afford 2,4-dimethoxy-benzoic acid hydrazide (3.31 g, 78%) as a white solid: 1 H NMR (CDCl 3 ) δ 8.77 (bs, 1H), 8.15 (d, J=8.8 Hz, 1H), 6.58 (dd, J=8.8, 2.2 Hz, 1H), 6.46 (d, J=2.2 Hz, 1H), 4.10 (bs, 2H), 3.91 (s, 3H), 3.83 (s, 3H). Ex-109B: A solution of 2,4-dimethoxy-benzoic acid hydrazide (Ex-109A, 1.0 g, 5.1 mmol) and isobutyl-isothiocyanate (0.70 g, 6.1 mmol) in ethanol (30 mL) was refluxed for 8 hours. The precipitate was filtered, washed with ethanol, dried in vacuo to afford 1-(2,4-dimethoxy-benzoyl)amino-3-isobutyl-thiourea (1.43 g). Additional product (0.1 g, 96% overall) was obtained by concentrating the mother liquid. 1 H NMR (CDCl 3 ) δ 10.71 (bs, 1H), 9.23 (bs, 1H), 8.03 (d, J=8.6 Hz, 1H), 6.98 (bs, 1H), 6.59 (dd, J=8.6, 2.6 Hz, 1H), 6.51 (d, J=2.6 Hz, 1H), 4.02 (s, 3H), 3.86 (s, 3H), 3.41 (dd, J=6.4, 6.6 Hz, 2H), 1.96–1.87 (m, 1H), 0.91 (d, J=6.5 Hz, 6H). Ex-109C: A solution of 1-(2,4-dimethoxy-benzoyl)amino-3-isobutyl-thiourea (Ex-109B, 0.5 g, 1.61 mmol) and sodium hydroxide (0.999M, 4.8 mL, 4.8 mmol) in ethanol (30 mL) was refluxed for one day. The solvent was removed under reduced pressure and the residue redissolved in ethyl acetate. The solution of ethyl acetate was washed with water and brine, dried over sodium sulfate, and concentrated to give 5-(2,4-dimethoxy-phenyl)-4-isobutyl-4H-[1,2,4]triazole-3-thiol (0.1 g). Additional product (0.36 g, 98% overall) was obtained by extracting the water wash with dichloromethane and a mixture of isopropyl alcohol (33%, v/v, in dichloromethane). 1 H NMR (CDCl 3 ) δ 10.82 (bs, 1H), 7.24 (d, J=8.1 Hz, 1H), 6.56 (dd, J=8.1, 2.4 Hz, 1H), 6.51 (d, J=2.4 Hz, 1H), 3.85 (s, 3H), 3.77 (s, 3H), 3.72 (d, J=6.7 Hz, 2H), 2.17–2.08 (m, 1H), 0.70 (d, J=6.7 Hz, 6H). Ex-109D: To a solution of 5-(2,4-dimethoxy-phenyl)-4-isobutyl-4H-[1,2,4]triazole-3-thiol (Ex-109C, 0.1 g, 0.34 mmol) in ethanol (10 mL) was added wet Raney Ni (0.27 g, 4.6 mmol). The suspension of ethanol was refluxed overnight and then passed through a bed of Hyflo Super Gel and diatomaceous earth. The filtrate was concentrated to afford 3-(2,4-dimethoxy-phenyl)-4-isobutyl-4H-[1,2,4]triazole (0.09 g, 100%) as a white solid: 1 H NMR (CDCl 3 ) δ 8.15 (s, 1H), 7.34 (d, J=7.8 Hz, 1H), 6.57 (dd, J=7.8, 2.3 Hz, 1H), 6.51 (d, J=2.3 Hz, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 3.62 (d, J=7.5 Hz, 2H), 1.89–1.80 (m, 1H), 0.76 (d, J=6.6 Hz, 6H). Ex-109E: To a solution of 3-(2,4-dimethoxy-phenyl)-4-isobutyl-4H-[1,2,4]triazole (Ex-109D, 0.78 g, 2.98 mmol) was added dichloromethyl methyl ether (0.4 mL, 4.48 mmol) followed by addition of titanium tetrachloride (1.0M in dichloromethane, 9.0 mL, 9.0 mmol) over 10 min at 0° C. The reaction mixture was allowed to stir at 0° C. for 30 min and ambient temperature overnight. The reaction mixture was poured into ice. The aqueous solution was extracted with dichloromethane and isopropyl alcohol (33%, v/v, in dichloromethane). The combined dichloromethane and isopropyl alcohol were washed with brine, dried over sodium sulfate and concentrated. The aqueous solution was treated with sodium hydroxide to pH 12 and extracted again with isopropyl alcohol (33%, v/v, in dichloromethane) to give additional product. The crude product was purified by flash chromatography. Elution with methanol (10%, v/v, in dichloromethane) afford 5-(4-isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-benzaldehyde (0.24 g, 28%): 1 H NMR (CDCl 3 ) δ 10.30 (s, 1H), 8.17 (s, 1H), 7.90 (s, 1H), 6.51 (s, 1H), 4.00 (s, 3H), 3.87 (s, 3H), 3.58 (d, J=7.2 Hz, 2H), 1.91–1.80 (m, 1H), 0.77 (d, J=6.5 Hz, 6H). To a solution of 4-acetyl-benzenesulfonamide (Ex-26A, 0.12 g, 0.62 mmol) and 5-(4-isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-benzaldehyde (Ex-109E, 0.18 g, 0.62 mmol) in N,N-dimethylformamide (9 mL) was added lithium methoxide (1.0M in methanol, 2.4 mL, 2.4 mmol). The solution was allowed to stir overnight. The reaction was quenched with water. The aqueous solution was washed ethyl acetate, acidified to pH 5, extracted with dichloromethane, isopropyl alcohol (33%, v/v, in dichloromethane). The combined dichloromethane and isopropyl alcohol was washed with brine, dried over sodium sulfate and concentrated. The crude product was then stirred in ethanol (50%, v/v, in acetone) to give the title compound as a light yellow solid: m.p.>240° C. 1 H NMR (DMSO-d 6 ) δ 8.60 (s, 1H), 8.26 (d, J=8.1 Hz, 2H), 8.06 (d, J=15.3 Hz, 1H), 8.07 (s, 1H), 7.91 (d, J=8.1 Hz, 2H), 7.84 (d, J=15.3 Hz, 1H), 7.50 (s, 1H), 6.84 (s, 1H), 4.01 (s, 3H), 3.87 (s, 3H), 3.61 (d, J=7.3 Hz, 2H), 1.81–1.74 (m, 1H), 0.67 (d, J=16.7 Hz, 6H). MS m/z=471 ([M+H] + , 100%). Example 110 4-{3E-[5-(4-Isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzoic acid To a solution of 4-acetyl-benzoic acid (0.12 g, 0.75 mmol) and 5-(4-isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-benzaldehyde (Ex-109E, 0.24 g, 0.83 mmol) in N,N-dimethylformamide (6 mL) was added lithium methoxide (1.0M in methanol, 3.0 mL, 3.0 mmol). The solution was allowed to stir overnight and additional lithium methoxide (0.11 g, 2.8 mmol). The reaction was quenched with water after 20 hours. The aqueous solution was washed ethyl acetate, acidified to pH 4. The precipitate was filtered, washed with ethanol and dried in vacuo to afford the title compound as a light yellow solid: m.p.>240° C. (dec.). 1 H NMR (DMSO-d 6 ) δ 8.59 (s, 1H), 8.18 (d, J=7.9 Hz, 2H), 8.07 (s, 1H), 8.04–8.01 (m, 3H), 7.85 (d, J=15.7 Hz, 1H), 6.84 (s, 1H), 4.06 (s, 3H), 3.92 (s, 3H), 3.66 (d, J=7.2 Hz, 2H), 1.87–1.74 (m, 1H), 0.72 (d, J=6.7 Hz, 6H). MS m/z=436 ([M+H] + , 100%). Example 111 4-{3E-[5-(2-Cyclopropyl-1H-imidazol-4-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide To a solution of 4-acetyl-benzenesulfonamide (Ex-26A, 0.12 g, 0.59 mmol) and 5-(2-cyclopropyl-1H-imidazol-4-yl)-2,4-dimethoxy-benzaldehyde (Ex-105B, 0.16 g, 0.59 mmol) in N,N-dimethylformamide (16 mL) was added lithium methoxide (1.0M in methanol, 2.4 mL, 2.4 mmol). The reaction mixture was allowed to stir for 18 hours at ambient temperature. The reaction was quenched with water. The aqueous solution was extracted with dichloromethane. The combined dichloromethane was concentrated. The crude product was purified by flash chromatography. Elution with methanol (10%, v/v, in dichloromethane) gave the title compound as red solid: m.p. 156–160° C. 1 H NMR (DMSO-d 6 ) δ 11.65 (bs, 1H), 8.32 (s, 1H), 8.19 (d, J=9.0 Hz, 2H), 8.00 (d, J=15.7 Hz, 1H), 7.95 (d, J=9.0 Hz, 2H), 7.62–7.52 (m, 2H), 7.24 (bs, 1H), 6.73 (s, 1H), 3.96 (s, 3H), 3.94 (s, 3H), 1.98–1.94 (m, 1H), 0.88–0.85 (m 4H). MS m/z=454 ([M+H] + , 100%). Example 112 4-{3E-[5-(3H-Imidazo[4,5-b]pyridin-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide The title compound was prepared by condensing 5-(3H-imidazo[4,5-b]pyridin-2-yl)-2,4-dimethoxy-benzaldehyde (Ex-76A) with 4-acetyl-benzenesulfonamide (Ex-26A) in a similar manner as described in Ex-22. Yellow solid, 26% yield, mp>260° C. 1 H-NMR (DMSO-d6) δ 8.73 (s, 1H), 8.31 (dd, J=1, 4 Hz, 1H), 8.26 (d, J=8 Hz, 2H), 8.05 (d, J=16 Hz, 1H), 7.89–7.97 (m, 3H), 7.82 (d, J=16 Hz, 1H), 7.17–7.21 (m, 1H), 6.89 (s, 1H), 4.09 (s, 3H), 4.03 (s, 3H). MS m/z=465([M+H] + , 65%), 256 (100%). HRMS (ES+) Calcd. for C 23 H 20 N 4 O 5 S: 465.1232. Found: 465.1240. Example 113 4-{3E-[2-(1H-Benzoimidazol-2-ylmethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide Ex-113A: 2-(1H-Benzoimidazol-2-ylmethoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-29C. Off-white solid, 67% yield, mp 230° C. (dec). 1 H-NMR (300 MHz, DMSO-d 6 ) □ 10.44 (s, 1H), 8.00 (s, 1H), 7.79–7.84 (m, 2H), 7.49–7.57 (m, 4H), 7.16 (s, 1H), 7.12 (dd, 1H, J=5.4, 3.6 Hz), 5.91 (s, 2H), 4.07 (s, 3H). MS (ESI) m/z=365 ([M+H] + , 100%). Anal. Calcd. for C 20 H 17 ClN 2 O 3 S.⅓H 2 O: C, 59.04; H, 4.38; N, 6.88; S, 7.88. Found: C, 59.07; H, 4.25; N, 6.85; S, 7.77. The title compound was prepared by condensing 2-(1H-benzoimidazol-2-ylmethoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-113A) and 4-acetyl-benzenesulfonamide (Ex-26A) in a similar manner as described in Ex-22. Light orange solid, 56% yield, mp 235–237° C. (dec). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.27 (s, 1H), 8.19 (d, 2H, J=8.4 Hz), 8.11 (d, 1H, J=15.4 Hz), 7.98 (d, 1H, J=15.4 Hz), 7.89 (d, 2H, J=8.4 Hz), 7.66–7.70 (m, 3H), 7.53–7.55 (m, 3H), 7.22–7.27 (m, 2H), 7.12–7.15 (m, 2H), 5.59 (s, 2H), 4.01 (s, 3H). MS (ESI) m/z=546 ([M+H] + , 100%). Anal. Calcd. for C 28 H 23 N 3 O 5 S 2 : C, 61.64; H, 4.25; N, 7.70; S, 11.75. Found: C, 61.49; H, 4.47; N, 7.74; S, 11.58. Example 114 4-{3E-[4-Methoxy-2-(pyridin-2-ylmethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide Ex-114A: 4-Methoxy-2-(pyridin-2-ylmethoxy)-5-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-29C. Yellow solid, 93% yield, mp 93–94° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.49 (s, 1H), 8.62 (d, 1H, J=5.1 Hz), 8.13 (s, 1H), 7.77 (dt, 1H, J=7.5, 1.5 Hz), 7.58 (d, 1H, J=7.5 Hz), 7.44 (dd, 1H, J=3.6, 1.5 Hz), 7.28–7.31 (m, 2H), 7.07 (dd, 1H, J=5.4, 3.6 Hz), 6.64 (s, 1H), 5.39 (s, 2H), 3.94 (s, 3H). MS (ESI) m/z=326 ([M+H] + , 100%). Anal. Calcd. for C 18 H 15 NO 3 S: C, 66.44; H, 4.65; N, 4.30; S, 9.85. Found: C, 66.43; H, 4.72; N, 4.37; S, 9.81. The title compound was prepared by condensing 4-methoxy-2-(pyridin-2-ylmethoxy)-5-thiophen-2-yl-benzaldehyde (Ex-114A) and 4-acetyl-benzenesulfonamide (Ex-26A) in a similar manner as described in Ex-22. Yellow solid, 90% yield, mp 188–189° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.66 (d, 1H, J=3.6 Hz), 8.28 (s, 1H), 8.21 (d, 2H, J=7.8 Hz), 8.11 (d, 1H, J=15.4 Hz), 7.89–7.99 (m, 4H), 7.57–7.68 (m, 4H), 7.53 (dd, 1H, J=5.4, 1.5 Hz), 7.41–7.45 (m, 1H), 7.13 (dd, 1H, J=5.4, 3.6 Hz), 7.02 (s, 1H), 5.45 (s, 2H), 3.99 (s, 3H). MS (ESI) m/z=507 ([M+H] + , 100%). Anal. Calcd. for C 26 H 22 N 2 O 5 S 2 .½H 2 O: C, 60.57; H, 4.50; N, 5.43; S, 12.44. Found: C, 60.92; H, 4.54; N, 5.48; S, 12.32. Example 115 4-{3E-[2-(Benzotriazol-1-ylmethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide Ex-115A: 2-(Benzotriazol-1-ylmethoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde was prepared in a similar manner as described in Ex-29C. Off-white solid, 92% yield, mp 137–138° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.30 (s, 1H), 8.10 (d, 1H, J=8.1 Hz), 8.06 (s, 1H), 7.75 (d, 1H, J=8.1 Hz), 7.57–7.62 (m, 1H), 7.40–7.48 (m, 2H), 7.30 (d, 1H, J=5.1 Hz), 7.08 (s, 1H), 7.05 (dd, 1H, J=5.1, 3.6 Hz), 6.74 (s, 2H), 4.01 (s, 3H). MS (ESI) m/z=366 ([M+H] + , 100%). Anal. Calcd. for C 19 H 15 N 3 O 3 S: C, 62.45; H, 4.14; N, 11.50; S, 8.78. Found: C, 62.69; H, 4.30; N, 11.52; S, 8.62. The title compound was prepared by condensing 2-(benzotriazol-1-ylmethoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-115A) and 4-acetyl-benzenesulfonamide (Ex-26A) in a similar manner as described in Ex-22. Light yellow solid, 56% yield, mp 255° C. (dec). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.21 (s, 1H), 8.09 (d, 3H, J=9.4 Hz), 8.01 (d, 1H, J=7.8 Hz), 7.93 (d, 2H, J=7.8 Hz), 7.75 (d, 2H, J=9.4 Hz), 7.56–7.69 (m, 4H), 7.42–7.47 (m, 1H), 7.38 (s, 1H), 7.13 (dd, 1H, J=5.4, 3.6 Hz), 7.05 (s, 2H), 4.05 (s, 3H). MS (ESI) m/z=547 ([M+H] + , 100%). Anal. Calcd. C 27 H 22 N 4 O 5 S 2 : C, 59.33; H, 4.06; N, 10.25; S, 11.73. Found: C, 59.45; H, 4.27; N, 9.92; S, 11.27. Example 116 4-{3E-[2,4-Dimethoxy-5-(1-methyl-1H-indol-2-yl)-phenyl]-acryloyl}-benzoic acid Ex-116A: To a solution of N-methyl indole (1.3 g, 10 mmol) in 50 ml THF, t-BuLi (1.7 m in THF, 7.1 ml, 12 mmol) was slowly added at 0° C. under nitrogen. The mixture was stirred at room temperature for 1 hr, BEt 3 (1.0 M in THF, 12 ml, 12 mmol) was added, and the mixture stirred for another 1 hr at room temperature. Then, PdCl 2 (PPh 3 ) 2 (0.35 g, 0.5 mmol) and 5-bromo-2,4-dimethoxybenzaldehyde (3.7 g, 15 mmol) were added, and the mixture was heated to about 60° C. for 30 minutes. The reaction mixture was poured into 50 ml 10% NaOH and treated with 30% H 2 O 2 and then stirred for 10 minutes. The mixture was extracted with EtOAc and combined organic phase was washed with H 2 O and brine, dried over MgSO4, and absorbed to small amount of silica gel. Column chromatography (EtOAc:Hexane, 1:2) gave 0.72 g (25%) 2,4-dimethoxy-5-(1-methyl-1H-indol-2-yl)-benzaldehyde. 1 H-NMR (CDCl 3 ) δ 10.33 (s, 1H), 7.84 (s, 1H), 7.60 (d, J=8 Hz, 1H), 7.31 (d, J=8 Hz, 1H), 7.18–7.24 (m, 1H), 7.07–7.12 (m, 1H), 6.53 (s, 1H), 6.46 (s, 1H), 4.00 (s, 3H), 3.89 (s, 3H), 3.53 (s, 3H). HRMS (EI) Calcd. for C 18 H 17 NO 3 : 295.1208. Found: 295.1202. The title compound was prepared by condensing 4-acetylbenzoic acid and 2,4-dimethoxy-5-(1-methyl-1H-indol-2-yl)-benzaldehyde (Ex-116A) in a similar manner as described in Ex-3. Yellow solid, 87% yield, mp 157–160° C. 1 H-NMR (DMSO-d6) δ 8.17 (d, J=8 Hz, 2H), 8.08 (d, J=15 Hz, 1H), 7.99–9.02 (m 3H), 7.83 (d, J=15 Hz, 1H), 7.52 (d, J=8 Hz, 1H), 7.42 (d, J=8 Hz, 1H), 7.10–7.15 (m, 1H), 6.99–7.04 (m, 1H), 6.85 (s, 1H), 6.42 (s, 1H), 4.01 (s, 3H), 3.88 (s, 3H), 3.50 (s, 3H). MS m/z=442 ([M+H] + , 100%). HRMS (ES+) Calcd. for C 27 H 23 NO 5 : 442.1654. Found: 442.1633. Example 117 4-{3E-[2,4-Dimethoxy-5-(1-methyl-1H-indol-2-yl)-phenyl]-acryloyl}-benzenesulfonamide The title compound was prepared by condensing 4-acetyl-benzenesulfonamide (Ex-26A) and 2,4-dimethoxy-5-(1-methyl-1H-indol-2-yl)-benzaldehyde (Ex-116A) in a similar manner as described in Ex-3. Yellow solid, 90% yield, mp 148–150° C. 1 H-NMR (CDCl 3 ) δ 8.17 (d, J=16 Hz, 1H), 8.09 (d, J=9 Hz, 2H), 8.01 (d, J=9 Hz, 2H), 7.68 (s, 1H), 7.64 (d, J=8 Hz, 1H), 7.47 (d, J=16 Hz, 1H), 7.35 (d, J=8 Hz, 1H), 7.22–7.26 (m, 1H), 7.11–7.16 (m, 1H), 6.58 (s, 1H), 6.50 (s, 1H), 4.92 (br, 2H), 4.02 (s, 3H), 3.90 (s, 3H), 3.58 (s, 3H). MS m/z=477 ([M+H] + , 100%). HRMS (ES+) Calcd. for C 26 H 24 NO 5 S: 477.1484. Found: 477.1487. Example 118 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid methyl ester The title compound was prepared by esterification of 4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid (Ex-3) with methanol in the presence of EDCI and DMAP. Yellow solid, 34% yield, m.p. 149–151° C. 1 H-NMR (300 MHz, CDCl 3 ): 8.17 (d, 2H, J=6.7 Hz), 8.10 (d, 1H, J=15.8 Hz), 8.05 (d, 2H, J=6.7 Hz), 7.95 (s, 1H), 7.82 (m, 2H), 7.67 (s, 1H), 7.57 (d, 1H, J=15.8 Hz), 7.33 (m, 2H), 6.58 (s, 1H), 4.04 (s, 3H), 4.00 (s, 3H), 3.97 (s, 3H). MS m/z=458 ([M] + , 100%). HRMS (EI) Calcd. for C 27 H 22 O 5 S: 458.118 Found: 458.1196. Example 119 4-{3-[3E-(2,3-Dihydro-furan-2-yl)-phenyl]-acryloyl}-benzenesulfonamide Ex-119A: 5-Bromobenzaldehyde (0.5 g, 2.7 mmol) and 2,3-dihydrofuran (0.56 g, 8.1 mmol) were dissolved in dioxane (5.0 mL). Nitrogen was bubbled into the solution for 15 min followed by the sequential addition of cesium carbonate (0.96 g, 2.9 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.014 g, 0.027 mmol). The solution was immediately heated to 45° C. and aged for 24 h. Upon completion, as determined by HPLC, the reaction was diluted with water (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over sodium sulfate and concentrated to a brown oil. Silica gel chromatography (ethyl acetate/hexanes, 1:9) gave 0.18 g (40%) of 3-(2,3-dihydro-furan-2-yl)-benzaldehyde as a clear, colorless oil. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.03 (s, 1H), 7.88 (s, 1H), 7.82 (d, 1H, J=7.2 Hz), 7.62–7.64 (m, 1H), 7.53 (t, 1H, J=7.2 Hz), 6.48 (q, 1H, J=Hz), 5.60 (dd, 1H, J=8.1, 10.8 Hz), 4.98 (q, 1H, J=3.3 Hz), 3.15 (ddt, 1H, J=15.0, 8.1, 2.5 Hz), 2.59 (ddt, 1H, J=15.0, 8.1, 2.5 Hz). MS (EI) m/z=174 ([M] + , 100%). HRMS (EI) Calcd. for C 11 H 10 O 2 : 174.0681. Found: 174.0677. The title compound was prepared by condensing 4-acetyl-benzenesulfonamide (Ex-26A) and 3-(2,3-dihydro-furan-2-yl)-benzaldehyde (Ex-119A) in a similar manner as described in Ex-3. Tan solid, 40% yield, mp 152–153° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.31 (d, 2H, J=7.5 Hz), 7.99 (d, 2H, J=7.5 Hz), 7.95 (d, 1H, J=15.8 Hz), 7.85 (brs, 3H), 7.78 (d, 1H, J=15.8 Hz), 7.57 (brs, 1H), 7.44–7.52 (m, 2H), 6.62 (q, 1H, J=2.4 Hz), 5.58 (dd, 1H, J=8.7, 10.8 Hz), 5.59 (q, 1H, J=2.4 Hz), 3.10 (ddt, 1H, J=15.0, 8.1, 2.5 Hz), 2.54 (ddt, 1H, J=15.0, 8.1, 2.5 Hz). MS (ESI) m/z=356 ([M+H] + , 100%). Anal. Calcd. for C 19 H 17 NO 4 S.⅕H 2 O: C, 63.56; H, 4.89; N, 3.90; S, 8.93. Found: C, 63.64; H, 4.88; N, 4.00; S, 8.71. Example 120 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid, N-methyl-D-glucamine salt 4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid of Ex. 3 was then made into a meglumine salt by suspending the 4-[3E-(5-benzo[b]thien-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid (4.45 g, 10 mmol) and N-methyl-D-glucamine (1.95 g, 10 mmol) in THF (100 mL). The mixture was stirred at room temperature for 5 minutes. Then, ethanol (100 mL) was added. This mixture was stirred at room temperature for 30 minutes. THF (20 mL) and ethanol (20 mL) were added and the mixture was heated slightly until it became a solution. This solution was stirred for 30 minutes and evaporated to a yellow foam. Crystallization from methanol gave the desired 4-[3E-(5-benzo[b]thien-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid N-methyl-D-glucamine salt as a yellow solid (4 g, 63%), mp 75–80° C. (changing forms). 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.14 (d, 2H), 8.02–8.10 (m, 3H), 7.94–7.98 (m, 3H), 7.86 (d, 1H), 7.36 (m, 2H), 6.89 (s, 1H), 4.06 (s, 3H), 4.04 (s, 3H), 3.94 (m, 1H), 3.71 (d, 1H), 3.61 (m, 1H), 3.39–3.55 (m, 3H), 3.04 (m, 1H), 2.95 (m, 1H), 2.54 (s, 3H). Anal. Calculated for C 33 H 37 NO 10 S.1.3H 2 O: C, 59.77; H, 6.02; N, 2.11; S, 4.84; found: C, 59.84; H, 5.75; N, 2.05; S, 4.70; Parent EIMS m/z=443 (M + ). Using the above procedure for producing the meglumine salt or procedures well known in the art, any of the compounds of the invention can be likewise made into a hydroxyl amine salt and in particular the meglumine salt. Example 121 4-{3E-[5-(2,5-Dihydro-furan-2-yl)-2,4-dimethoxy-phenyl]-acryloyl}-benzenesulfonamide Ex-121A: 5-Bromo-2,4-dimethoxybenzaldehyde (1.0 g, 4.0 mmol) and 2,3-dihydrofuran (0.85 g, 12.2 mmol) were dissolved in dioxane (10.0 mL). Nitrogen was bubbled into the solution for 15 min followed by the sequential addition of cesium carbonate (1.4 g, 4.5 mmol) and bis(tri-t-butylphosphine)palladium (0) (0.021 g, 0.041 mmol). The solution was immediately heated to 45° C. and aged for 72 h. Additional equivalents of cesium carbonate (0.70 g, 2.1 mmol), 2,3-dihydrofuran (0.85 g, 12.2 mmol), and Pd catalyst (0.0021 g, 0.0041 mmol) were added after 24 h and 48 h to drive the reaction to completion. Upon completion, as determined by HPLC, the reaction was diluted with water (30 mL) and extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over sodium sulfate and concentrated to an orange oil. Silica gel chromatography (ethyl acetate/hexanes, 1:2) afforded 0.32 g (50%) of 5-(2,5-dihydro-furan-2-yl)-2,4-dimethoxy-benzaldehyde as a pale yellow solid, mp 84–85° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.29 (s, 1H), 7.79 (s, 1H), 6.42 (s, 1H), 5.99–6.06 (m, 2H), 5.89–5.92 (m, 1H), 4.80–4.87 (m, 1H), 4.71–4.77 (m, 1H), 3.95 (s, 3H), 3.92 (s, 3H). MS (EI) m/z=234 ([M] + , 100%). Anal. Calcd. C 13 H 14 O 4 : C, 66.66; H, 6.02. Found: C, 66.49; H, 6.08. 5-(2,5-Dihydro-furan-2-yl)-2,4-dimethoxy-benzaldehyde (Ex-121A, 0.10 g, 0.43 mmol) and 4-acetylbenzenesulfonamide (Ex-26A, 0.085 g, 0.43 mmol) were dissolved in a dimethylformamide-methanol solution (2.9 mL, 7:3). After complete dissolution, lithium methoxide (0.065 g, 1.7 mmol) was added and the resulting orange slurry was stirred in the dark at room temperature for 4 h. Upon completion, as determined by HPLC, the mixture was diluted with water (15 mL) and extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was taken up in ethanol (2 mL) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. The resulting precipitate was collected on filter paper and dried in vacuo to yield 0.13 g (70%) of the title compound as a yellow solid, mp 194–195° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.23 (d, 2H, J=8.2 Hz), 8.03 (d, 1H, J=15.3 Hz), 7.97 (d, 2H, J=8.2 Hz), 7.69 (s, 1H), 7.65 (d, 1H, J=15.3 Hz), 7.55 (brs, 2H), 6.73 (s, 1H), 6.06–6.09 (m, 1H), 5.90–5.98 (m, 2H), 4.86–4.92 (m, 1H), 4.63–4.68 (m, 1H), 3.96 (s, 3H), 3.92 (s, 3H). MS (ESI) m/z=416 ([M+H] + , 100%). Anal. Calcd. C 21 H 21 NO 6 S: C, 60.71; H, 5.09; N, 3.37; S, 7.72. Found: C, 60.95; H, 5.24; N, 3.46; S, 7.72. Example 122 4-{3E-[4-Methoxy-2-(6-methyl-pyridin-2-yloxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzenesulfonamide Ex-122A: To a solution of 2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde (0.68 g, 2.9 mmol) and 2-bromo-6-methylpyridine (0.25 g, 1.4 mmol) in toluene (1.0 mL) was added ethyl acetate (0.0063 g, 0.072 mmol, 1-naphthoic acid (0.50 g, 2.9 mmol), 5 Å molecular sieves (0.36 g), cesium carbonate (0.94 g, 2.9 mmol), and copper(I) triflate-benzene complex (0.020 g, 0.036 mmol). The phenoxide crashed out of solution upon addition of cesium carbonate and additional toluene (1 mL) was added to facilitate stirring. The heterogeneous solution was immediately heated to 110° C. and aged for 24 h. Upon completion, as determined by HPLC, the reaction was diluted with a 5% sodium hydroxide solution (10 mL) and ethyl acetate (10 mL) and stirred for 30 min. The layers were separated and the aqueous layer was extracted with ethyl acetate (5×20 mL). The combined organic extracts were washed with a 50% brine solution (1×25 mL), brine (1×25 mL), dried over sodium sulfate and concentrated to an dark brown semi-solid. Silica gel chromatography (ethyl acetate/hexanes, 1:4) afforded 0.30 g (65%) of 4-methoxy-2-(6-methyl-pyridin-2-yloxy)-5-thiophen-2-yl-benzaldehyde as a light orange solid, mp 140–141° C. 1 H-NMR (300 MHz, CDCl 3 ) δ 10.21 (s, 1H), 8.23 (s, 1H), 7.64 (dd, 1H, J=7.8, 7.2 Hz), 7.52 (d, 1H, J=3.3 Hz), 7.35 (d, 1H, J=5.1 Hz), 7.10 (dd, 1H, J=5.1, 3.3 Hz), 6.94 (d, 1H, J=7.2 Hz), 6.78 (d, 1H, J=7.8 Hz), 6.75 (s, 1H), 3.92 (s, 3H), 2.44 (s, 3H). HRMS (EI) Calcd. for C 18 H 15 NO 3 S: 325.0773. Found: 325.0775. Anal. Calcd. C 18 H 15 NO 3 S: C, 66.44; H, 4.65; N, 4.30; S, 9.85. Found: C, 60.00; H, 4.58; N, 4.05; S, 9.84. 4-Methoxy-2-(6-methyl-pyridin-2-yloxy)-5-thiophen-2-yl-benzaldehyde (Ex-122A, 0.20 g, 0.62 mmol) and 4-acetylbenzenesulfonamide (Ex-26A, 0.12 g, 0.62 mmol) were dissolved in a dimethylformamide-methanol solution (4.2 mL, 7:3). After complete dissolution, lithium methoxide (0.093 g, 2.5 mmol) was added and the resulting orange slurry was stirred in the dark at room temperature for 3 h. Upon completion, as determined by HPLC, the mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was taken up in ethanol (2 mL) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. The resulting precipitate was collected on filter paper and dried in vacuo to yield 0.25 g (82%) of the title compound as a yellow solid, mp 164–165° C. 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.47 (s, 1H), 8.24 (d, 2H, J=8.1 Hz), 7.98 (d, 1H, J=15.3 Hz), 7.96 (d, 2H, J=8.1 Hz), 7.78–7.85 (m, 2H), 7.77 (d, 1H, J=15.3 Hz), 7.62 (d, 1H, J=5.1 Hz), 7.57 (s, 2H), 7.19 (dd, 1H, J=5.1, 3.6 Hz), 7.04 (d, 1H, J=7.5 Hz), 6.99 (s, 1H), 6.91 (d, 1H, J=8.4 Hz), 3.90 (s, 3H), 2.33 (s, 3H). Anal. Calcd. C 26 H 22 N 2 O 5 S 2 : C, 61.64; H, 4.38; N, 5.53; S, 12.66. Found: C, 61.88; H, 4.47; N, 5.59; S, 12.62. Example 123 5-Iodo-2,4-dimethoxy-benzaldehyde To a solution of 2,4-dimethoxy-benzaldehyde (20.0 g, 120.4 mmol) in methanol (550 mL) was added a solution of iodine monochloride (23.25 g, 144.9 mmol) in methanol (60 mL) dropwise over 20 min. The solution was allowed to stir at ambient temperature for 3 hours and then poured into a solution of hydrochloric acid (0.5 M, 600 mL). The resulting precipitate was collected by filtration, washed with water, and dried in vacuo. The crude product was further recrystallized from a mixture of tetrahydrofuran and heptane (1:1, v/v) to give the title compound as a white solid (30.62 g, 87.5%), m.p. 170–172° C. 1 H NMR (CDCl 3 ) δ 10.19 (s, 1H), 8.22 (s, 1H), 6.39 (s, 1H), 3.97 (s, 3H), 3.95 (s, 3H). Example 124 5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-benzaldehyde Ex-123A: Potassium fluoride (0.42 g, 7.2 mmol), 5-iodo-2,4-dimethoxy-benzaldehyde (Ex-123, 1.0 g, 3.42 mmol), 2-benzo[b]thiophene boronic acid (0.67 g, 3.77 mmol), degased tetrahydrofuran (10 mL), tris(dibenzylideneacetone)dipalladium (19 mg, 0.02 mmol), and tri-tert-butylphosphine (100 mg, 0.05 mmol) were sequentially charged into a flask equipped with a condenser and nitrogen inlet adapter. The reaction mixture was heated at 60° C. for one hour under nitrogen. HPLC analysis indicated of 100% conversion of 5-iodo-2,4-dimethoxy-benzaldehyde (Ex-123) to the title compound prepared through another route (Ex-3A). Using one or more of the preceding methods, additional substituted 1-[2,2-bis(hydroxymethyl)-benzo[1,3]dioxol-5-yl]-3-[(heteroaryl or heterocyclic)phenyl]-2-propen-1-ones, 4-[3-{(heteroaryl or heterocyclic)phenyl}acryloyl]-benzoic acids, 1-[(amino)phenyl]-3-[(heteroaryl or heterocyclic)phenyl]-2-propen-1-ones, 4-[3-{(heteroaryl or heterocyclic)-phenyl}-3-oxo-propenyl]-benzoic acids, 1-(1H-indol-5-yl)-3-{(heteroaryl or heterocyclic)-phenyl}-propen-2-ones, 1-[(heteroaryl or heterocyclic)phenyl]-3-phenyl-2-propen-1-ones, and substituted 3-[(heteroaryl or heterocyclic)phenyl]-1-phenyl-2-propen-1-ones can be prepared by one skilled in the art using similar methods, as shown in Example Tables 1 through 33. EXAMPLE TABLE 1Substituted 4-[3-{2-Isopropoxy-4-methoxy-(5-heteroaryl or 5-heterocyclic)phenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β200A200B201A201B202A202B203A203B204A204B205A205B206A206B207A207B208A208B209A209B210A210B211A211B212A212B213A213B214A214B215A215B216A216B217A217B218A218B219A219B220A220B221A221B222A222B223A223B224A224B225A225B226A226B227A227B228A228B229A229B230A230B231A231B232A232B233A233B234A234B235A235B236A236B237A237B238A238B239A239B240A240B241A241B242A242B243A243B244A244B245A245B246A246B247A247B248A248B249A249B250A250B251A251B252A252B253A253B254A254B255A255B256A256B257A257B258A258B259A259B260A260B261A261B262A262B EXAMPLE TABLE 12Substituted 4-[3-{2-Cyclopropylmethoxy-4-methoxy-(5-heteroaryl or5-heterocyclic)phenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β263A263B264A264B265A265B266A266B267A267B268A268B269A269B270A270B271A271B272A272B273A273B274A274B275A275B276A276B277A277B278A278B279A279B280A280B281A281B282A282B283A283B284A284B285A285B286A286B287A287B288A288B289A289B290A290B291A291B292A292B293A293B294A294B295A295B296A296B297A297B298A298B299A299B300A300B301A301B302A302B303A303B304A304B305A305B306A306B307A307B308A308B309A309B310A310B311A311B312A312B313A313B314A314B315A315B316A316B317A317B318A318B319A319B320A320B321A321B322A322B323A323B324A324B325A325B326A326B327A327B328A328B329A329B330A330B331A331B332A332B333A333B334A334B EXAMPLE TABLE 3Substituted 4-[3-{2,4-dimethoxy-(6-Heteroaryl or 6-heterocyclic)phenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β335A335B336A336B337A337B338A338B339A339B340A340B341A341B342A342B343A343B344A344B345A345B346A346B347A347B348A348B349A349B350A350B351A351B352A352B353A353B354A354B355A355B356A356B357A357B358A358B359A359B360A360B361A361B362A362B363A363B364A364B365A365B366A366B367A367B368A368B369A369B370A370B371A371B372A372B373A373B374A374B375A375B376A376B377A377B378A378B379A379B380A380B381A381B382A382B383A383B384A384B385A385B386A386B387A387B388A388B389A389B390A390B391A391B392A392B393A393B394A394B395A395B396A396B397A397B EXAMPLE TABLE 4Substituted 1-(2,2-Bis-hydroxymethyl-benzo[1,3]dioxol-5-yl)-3-[2,4-dimethoxy-(5-heteroaryl or 5-heterocylic)phenyl]-2-propen-1-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β398A398B399A399B400A400B401A401B402A402B403A403B404A404B405A405B406A406B407A407B408A408B409A409B410A410B411A411B412A412B413A413B414A414B415A415B416A416B417A417B418A418B419A419B420A420B421A421B422A422B423A423B424A424B425A425B426A426B427A427B428A428B429A429B430A430B431A431B432A432B433A433B434A434B435A435B436A436B437A437B438A438B439A439B440A440B441A441B442A442B443A443B444A444B445A445B446A446B447A447B448A448B449A449B450A450B451A451B452A452B453A453B454A454B455A455B456A456B457A457B458A458B459A459B460A460B461A461A462A462B463A463B464A464B465A465B466A466B467A467B468A468B469A469B EXAMPLE TABLE 5Substituted 1-(3-Aminophenyl)-3-[2,4-dimethoxy-(5-heteroaryl or 5-heterocylic)phenyl]-2-propen-1-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β470A470B471A471B472A472B473A473B474A474B475A475B476A476B477A477B478A478B479A479B480A480B481A481B482A482B483A483B484A484B485A485B486A486B487A487B488A488B489A489B490A490B491A491B492A492B493A493B494A494B495A496B496A496B497A497B498A498B499A499B500A500B501A501B502A502B503A503B504A504B502A505B506A506B507A507B508A508B509A509B510A510B511A511B512A512B513A513B514A514B515A515B516A516B517A517B518A518B519A519B520A520B521A521B522A522B523A523B524A524B525A525B526A526B527A527B528A528B529A529B530A530B531A531B532A532B EXAMPLE TABLE 6Substituted 1-(4-Aminophenyl)-3-[2,4-dimethoxy-(5-heteroaryl or 5-heterocylic)phenyl]-2-propen-1-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β533A533B534A534B535A535B536A536B537A537B538A538B539A539B540A540B541A541B542A542B543A543B544A544B545A545B546A546B547A547B548A548B549A549B550A550B551A551B552A552B553A553B554A554B555A555B556A556B557A557B558A558B559A559B560A560B561A561B562A562B563A563B564A564B565A565B566A566B567A567B568A568B569A569B570A570B571A571B572A572B573A573B574A574B575A575B576A576B577A577B578A578B579A579B580A580B581A581B582A582B583A583B584A584B585A585B586A586B587A587B588A588B589A589B590A590B591A591B592A592B593A593B594A594B595A595B596A596B597A597B598A598B599A599B600A600B601A601B602A602B603A603B604A604B EXAMPLE TABLE 7Substituted 1-{4-(Pyrrolidin-1-yl)phenyl}-3-[2,4-dimethoxy-(5-heteroaryl or5-heterocylic)phenyl]-2-propen-1-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β605A605B606A606B607A607B608A608B609A609B610A610B611A611B612A612B613A613B614A614B615A615B616A616B617A617B618A618B619A619B620A620B621A621B622A622B623A623B624A624B625A625B626A626B627A627B628A628B629A629B630A630B631A631B632A632B633A633B634A634B635A635B636A636B637A637B638A638B639A639B640A640B641A641B642A642B643A643B644A644B645A645B646A646B647A647B648A648B649A649B650A650B651A651B652A652B653A653B654A654B655A655B656A656B657A657B658A658B659A659B660A660B661A661B662A662B663A663B664A664B665A665B666A666B667A667B EXAMPLE TABLE 8Substituted 1-{4-(Methanesulfonylamino)phenyl}-3-[2,4-dimethoxy-(5-heteroaryl or 5-heterocylic)phenyl]-2-propen-1-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β668A668B669A669B670A670B671A671B672A672B673A673B674A674B675A675B676A676B677A677B678A678B679A679B680A680B681A681B682A682B683A683B684A684B685A685B686A686B687A687B688A688B689A689B690A690B691A691B692A692B693A693B694A694B695A695B696A696B697A697B698A698B699A699B700A700B701A701B702A702B703A703B704A704B705A705B706A706B707A707B708A708B709A709B710A710B711A711B712A712B713A713B714A714B715A715B716A716B717A717B718A718B719A719B720A720B721A721B722A722B723A723B724A724B725A725B726A726B727A727B728A728B729A729B730A730B731A731B732A732B733A733B734A734B735A735B736A736B737A737B738A738B739A739B EXAMPLE TABLE 9Substituted 1-{4-(Methanesulfonylamino)phenyl}-3-[3,4-dimethoxy-(5-heteroaryl or 5-heterocylic)phenyl]-2-propen-1-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β740A740B741A741B742A742B743A743B744A744B745A745B746A746B747A747B748A748B749A749B750A750B751A751B752A752B753A753B754A754B755A755B756A756B757A757B758A758B759A759B760A760B761A761B762A762B763A763B764A764B765A765B766A766B767A767B768A768B769A769B770A770B771A771B772A772B773A773B774A774B775A775B776A776B777A777B778A778B779A779B780A780B781A781B782A782B783A783B784A784B785A785B786A786B787A787B788A788B789A789B790A790B791A791B792A792B793A793B794A794B795A795B796A796B797A797B798A798B799A799B800A800B801A801B802A802B EXAMPLE TABLE 10Substituted 1-{4-(Amino)phenyl}-3-[3,4-dimethoxy-(5-heteroaryl or 5-heterocylic)phenyl]-2-propen-1-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β803A803B804A804B805A805B806A806B807A807B808A808B809A809B810A810B811A811B812A812B813A813B814A814B815A815B816A816B817A817B818A818B819A819B820A820B821A821B822A822B823A823B824A824B825A825B826A826B827A827B828A828B829A829B830A830B831A831B832A832B833A833B834A834B835A835B836A836B837A837B838A838B839A839B840A840B841A841B842A842B843A843B844A844B845A845B846A846B847A847B848A848B849A849B850A850B851A851B852A852B853A853B854A854B855A855B856A856B857A857B858A858B859A859B860A860B861A861B862A862B863A863B864A864B865A865B866A866B867A867B868A868B869A869B870A870B871A871B872A872B873A873B874A874B EXAMPLE TABLE 11Substituted 1-{4-(Amino)phenyl}-3-[2,6-dimethoxy-(4-heteroaryl or 4-heterocylic)-phenyl]-2-propen-1-ones.ABEx. No.R 4βEx. No.R 4βEx. No.R 4β875A875B876A876B877A877B878A878B879A879B880A880B881A881B882A882B883A883B884A884B885A885B886A886B887A887B888A888B889A889B890A890B891A891B892A892B893A893B894A894B895A895B896A896B897A897B898A898B899A899B900A900B901A901B902A902B903A903B904A904B905A905B906A906B907A907B908A908B909A909B910A910B911A911B912A912B913A913B914A914B915A915B916A916B917A917B918A918B919A919B920A920B921A921B922A922B923A923B924A924B925A925B926A926B927A927B928A928B929A929B930A930B931A931B932A932B933A933B934A934B935A935B936A936B937A937B EXAMPLE TABLE 12Substituted 1-{4-(Methanesulfonylamino)phenyl}-3-[2,6-dimethoxy-(4-heteroaryl or 4-heterocylic)phenyl]-2-propen-1-ones.ABEx. No.R 4βEx. No.R 4βEx. No.R 4β938A938B939A939B940A940B941A941B942A942B943A943B944A944B945A945B946A946B947A947B948A948B949A949B950A950B951A951B952A952B953A953B954A954B955A955B956A956B957A957B958A958B959A959B960A960B961A961B962A962B963A963B964A964B965A965B966A966B967A967B968A968B969A969B970A970B971A971B972A972B973A973B974A974B975A975B976A976B977A977B978A978B979A979B980A980B981A981B982A982B983A983B984A984B985A985B986A986B987A987B988A988B989A989B990A990B991A991B992A992B993A993B994A994B995A995B996A996B997A997B998A998B999A999B1000A1000B1001A1001B1002A1002B1003A1003B1004A1004B1005A1005B1006A1006B1007A1007B1008A1008B1009A1009B EXAMPLE TABLE 13Substituted 1-(1H-Indol-5-yl)-3-{2,4-dimethoxy-5-(heteroaryl orheterocyclic)phenyl}-propen-2-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1010A1010B1011A1011B1012A1012B1013A1013B1014A1014B1015A1015B1016A1016B1017A1017B1018A1018B1019A1019B1020A1020B1021A1021B1022A1022B1023A1023B1024A1024B1025A1025B1026A1026B1027A1027B1028A1028B1029A1029B1030A1030B1031A1031B1032A1032B1033A1033B1034A1034B1035A1035B1036A1036B1037A1037B1038A1038B1039A1039B1040A1040B1041A1041B1042A1042B1043A1043B1044A1044B1045A1045B1046A1046B1047A1047B1048A1048B1049A1049B1050A1050B1051A1051B1052A1052B1053A1053B1054A1054B1055A1055B1056A1056B1057A1057B1058A1058B1059A1059B1060A1060B1061A1061B1062A1062B1063A1063B1064A1064B1065A1065B1066A1066B1067A1067B1068A1068B1069A1069B1070A1070B1071A1071B1072A1072B EXAMPLE TABLE 14Substituted 1-(1H-Indol-5-yl)-3-{3,4-dimethoxy-5-(heteroaryl orheterocyclic)phenyl}-propen-2-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1073A1073B1074A1074B1075A1075B1076A1076B1077A1077B1078A1078B1079A1079B1080A1080B1081A1081B1082A1082B1083A1083B1084A1084B1085A1085B1086A1086B1087A1087B1088A1088B1089A1089B1090A1090B1091A1091B1092A1092B1093A1093B1094A1094B1095A1095B1096A1096B1097A1097B1098A1098B1099A1099B1100A1100B1101A1101B1102A1102B1103A1103B1104A1104B1105A1105B1106A1106B1107A1107B1108A1108B1109A1109B1110A1110B1111A1111B1112A1112B1113A1113B1114A1114B1115A1115B1116A1116B1117A1117B1118A1118B1119A1119B1120A1120B1121A1121B1122A1122B1123A1123B1124A1124B1125A1125B1126A1126B1127A1127B1128A1128B1129A1129B1130A1130B1131A1131B1132A1132B1133A1133B1134A1134B1135A1135B1136A1136B1137A1137B1138A1138B1139A1139B1140A1140B1141A1141B1142A1142B1143A1143B1144A1144B EXAMPLE TABLE 15Substituted 1-(1H-1-Methyl-indol-5-yl)-3-{2,4-dimethoxy-5-(heteroaryl orheterocyclic)phenyl}-propen-2-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β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ubstituted 1-(1H-1-Methyl-indol-5-yl)-3-{3,4-dimethoxy-5-(heteroaryl orheterocyclic)phenyl}-propen-2-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1208A1208B1209A1209B1210A1210B1211A1211B1212A1212B1213A1213B1214A1214B1215A1215B1216A1216B1217A1217B1218A1218B1219A1219B1220A1220B1221A1221B1222A1222B1223A1223B1224A1224B1225A1225B1226A1226B1227A1227B1228A1228B1229A1229B1230A1230B1231A1231B1232A1232B1233A1233B1234A1234B1235A1235B1236A1236B1237A1237B1238A1238B1239A1239B1240A1240B1241A1241B1242A1242B1243A1243B1244A1244B1245A1245B1246A1246B1247A1247B1248A1248B1249A1249B1250A1250B1251A1251B1252A1252B1253A1253B1254A1254B1255A1255B1256A1256B1257A1257B1258A1258B1259A1259B1260A1260B1261A1261B1262A1262B1263A1263B1264A1264B1265A1265B1266A1266B1267A1267B1268A1268B1269A1269B1270A1270B1271A1271B1272A1272B1273A1273B1274A1274B1275A1275B1276A1276B1277A1277B1278A1278B1279A1279B EXAMPLE TABLE 17Substituted 4-[3-{2-(Pyrrolidin-1-yl)-(4-heteroaryl or 4-heterocyclic)-phenyl}-acryloyl]-benzoic Acids.ABEx. No.R 4βEx. No.R 4βEx. No.R 4β1280A1280B1281A1281B1282A1282B1283A1283B1284A1284B1285A1285B1286A1286B1287A1287B1288A1288B1289A1289B1290A1290B1291A1291B1292A1292B1293A1293B1294A1294B1295A1295B1296A1296B1297A1297B1298A1298B1299A1299B1300A1300B1301A1301B1302A1302B1303A1303B1304A1304B1305A1305B1306A1306B1307A1307B1308A1308B1309A1309B1310A1310B1311A1311B1312A1312B1313A1313B1314A1314B1315A1315B1316A1316B1317A1317B1318A1318B1319A1319B1320A1320B1321A1321B1322A1322B1323A1323B1324A1324B1325A1325B1326A1326B1327A1327B1328A1328B1329A1329B1330A1330B1331A1331B1332A1332B1333A1333B1334A1334B1335A1335B1336A1336B1337A1337B1338A1338B1339A1339B1340A1340B1341A1341B1342A1342B1343A1343B1344A1344B1345A1345B1346A1346B1347A1347B1348A1348B1349A1349B1350A1350B1351A1351B EXAMPLE TABLE 18Substituted 4-[3-{(5-Heteroaryl or 5-heterocyclic)-2,4-dimethoxyphenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1352A1352B1353A1353B1354A1354B1355A1355B1356A1356B1357A1357B1358A1358B1359A1359B1360A1360B1361A1361B1362A1362B1363A1363B1364A1364B1365A1365B1366A1366B1367A1367B1368A1368B1369A1369B1370A1370B1371A1371B1372A1372B1373A1373B1374A1374B1375A1375B1376A1376B1377A1377B1378A1378B1379A1379B1380A1380B1381A1381B1382A1382B1383A1383B1384A1384B1385A1385B1386A1386B1387A1387B1388A1388B1389A1389B1390A1390B1391A1391B1392A1392B1393A1393B1394A1394B1395A1395B1396A1396B1397A1397B1398A1398B1399A1399B1400A1400B1401A1401B1402A1402B1403A1403B1404A1404B1405A1405B1406A1406B1407A1407B1408A1408B1409A1409B1410A1410B1411A1411B1412A1412B1413A1413B1414A1414B EXAMPLE TABLE 19Substituted 3-[3-{(5-Heteroaryl or 5-heterocyclic)-2,4-dimethoxyphenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1415A1415B1416A1416B1417A1417B1418A1418B1419A1419B1420A1420B1421A1421B1422A1422B1423A1423B1424A1424B1425A1425B1426A1426B1427A1427B1428A1428B1429A1429B1430A1430B1431A1431B1432A1432B1433A1433B1434A1434B1435A1435B1436A1436B1437A1437B1438A1438B1439A1439B1440A1440B1441A1441B1442A1442B1443A1443B1444A1444B1445A1445B1446A1446B1447A1447B1448A1448B1449A1449B1450A1450B1451A1451B1452A1452B1453A1453B1454A1454B1455A1455B1456A1456B1457A1457B1458A1458B1459A1459B1460A1460B1461A1461B1462A1462B1463A1463B1464A1464B1465A1465B1466A1466B1467A1467B1468A1468B1469A1469B1470A1470B1471A1471B1473A1473B1474A1474B1475A1475B1476A1476B1477A1477B1478A1478B1479A1479B1480A1480B1481A1481B1482A1482B1483A1383B1484A1484B1485A1485B1486A1486B1487A1487B EXAMPLE TABLE 20Substituted 2-[3-{(5-Heteroaryl or 5-heterocyclic)-2,4-dimethoxyphenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1488A1488B1489A1489B1490A1490B1491A1491B1492A1492B1493A1493B1494A1494B1495A1495B1496A1496B1497A1497B1498A1498B1499A1499B1500A1500B1501A1501B1502A1502B1503A1503B1504A1504B1505A1505B1506A1506B1507A1507B1508A1508B1509A1509B1510A1510B1511A1511B1512A1512B1513A1513B1514A1514B1515A1515B1516A1516B1517A1517B1518A1518B1519A1519B1520A1520B1521A1521B1522A1522B1523A1523B1524A1524B1525A1525B1526A1526B1527A1527B1528A1528B1529A1529B1530A1530B1531A1531B1532A1532B1533A1533B1534A1534B1535A1535B1536A1536B1537A1537B1538A1538B1539A1539B1540A1540B1541A1541B1542A1542B1543A1543B1544A1544B1545A1545B1546A1546B1547A1547B1548A1548B1549A1549B1550A1550B EXAMPLE TABLE 21Substituted 2-[3-{(5-Heteroaryl or 5-heterocyclic)-2,4-dimethoxyphenyl}-acryloyl]-5-methanesulfonylamino-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1551A1551 B1552A1552B1553A1553B1554A1554B1555A1552B1556A1556B1557A1557B1558A1558B1559A1559B1560A1560B1561A1561B1562A1562B1563A1563B1564A1564B1565A1565B1566A1566B1567A1567B1568A1568B1569A1569B1570A1570B1571A1571B1572A1572B1573A1573B1574A1574B1575A1575B1576A1576B1577A1577B1578A1578B1579A1579B1580A1580B1581A1581B1582A1582B1583A1583B1584A1584B1585A1586B1586A1586B1587A1587B1588A1588B1589A1589B1590A1590B1591A1591B1592A1592B1593A1593B1594A1594B1595A1595B1596A1596B1597A1597B1598A1598B1599A1599B1600A1600B1601A1601B1602A1602B1603A1603B1604A1605B1605A1605B1606A1606B1607A1607B1608A1608B1609A1609B1610A1610B1611A1611B1612A1612B1613A1613B1614A1614B1615A1615B1616A1616B1617A1617B1618A1618B1619A1619B1620A1620B1621A1621B1622A1622B EXAMPLE TABLE 22Substituted 5-Amino-2-[3-{(5-heteroaryl or 5-heterocyclic)-2,4-dimethoxy-phenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1623A1623B1624A1624B1625A1625B1626A1626B1627A1627B1628A1628B1629A1629B1630A1630B1631A1631B1632A1632B1633A1633B1634A1634B1635A1635B1636A1636B1637A1637B1638A1638B1639A1639B1640A1640B1641A1641B1642A1642B1643A1643B1644A1644B1645A1645B1646A1646B1647A1647B1648A1648B1649A1649B1650A1650B1651A1651B1652A1652B1653A1653B1654A1654B1655A1655B1656A1656B1657A1657B1658A1658B1659A1659B1660A1660B1661A1661B1662A1662B1663A1663B1664A1664B1665A1665B1666A1666B1667A1667B1688A1688B1669A1669B1670A1670B1671A1671B1672A1672B1673A1673B1674A1674B1675A1675B1676A1676B1677A1677B1678A1678B1679A1679B1680A1680B1681A1681B1682A1682B1683A1683B1684A1684B1685A1685B EXAMPLE TABLE 23Substituted 4-[3-{(5-Heteroaryl or 5-heterocyclic)-3,4-dimethoxyphenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1686A1686B1687A1687B1688A1688B1689A1689B1690A1690B1691A1691B1692A1692B1693A1693B1694A1694B1695A1695B1696A1696B1697A1697B1698A1698B1699A1699B1700A1700B1701A1701B1702A1702B1703A1703B1704A1704B1705A1705B1706A1706B1707A1707B1708A1708B1709A1709B1710A1710B1711A1711B1712A1712B1713A1713B1714A1714B1715A1715B1716A1716B1717A1717B1718A1718B1719A1719B1720A1720B1721A1721B1722A1722B1723A1723B1724A1724B1725A1725B1726A1726B1727A1727B1728A1728B1729A1729B1730A1730B1731A1731B1732A1732B1733A1733B1734A1734B1735A1735B1736A1736B1737A1737B1738A1738B1739A1739B1740A1740B1741A1741B1742A1742B1743A1743B1744A1744B1745A1745B1746A1746B1747A1747B1748A1748B1749A1749B1750A1750B1751A1751B1752A1752B1753A1753B1754A1754B1755A1755B1756A1756B1757A1757B EXAMPLE TABLE 24Substituted 3-[3-{(5-Heteroaryl or 5-heterocyclic)-3,4-dimethoxyphenyl}-acryloyl]-5-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1758A1758 B1759A1759B1760A1760B1761A1761B1762A1762B1763A1763B1764A1764B1765A1765B1766A1766B1767A1767B1768A1768B1769A1769B1770A1770B1771A1771B1772A1772B1773A1733B1774A1774B1775A1775B1776A1776B1777A1777B1778A1778B1779A1779B1780A1780B1781A1781B1782A1782B1783A1783B1784A1784B1785A1785B1786A1786B1787A1787B1788A1788B1789A1789B1790A1790B1791A1791B1792A1792B1793A1793B1794A1794B1795A1795B1796A1796B1797A1797B1798A1798B1799A1799B1800A1800B1801A1801B1802A1802B1803A1803B1804A1804B1805A1805B1806A1806B1807A1807B1808A1808B1809A1809B1810A1810B1811A1811B1812A1812B1813A1813B1814A1814B1815A1815B1816A1816B1817A1817B1818A1818B1819A1819B1820A1820B EXAMPLE TABLE 25Substituted 2-[3-{(5-Heteroaryl or 5-heterocyclic)-3,4-dimethoxyphenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1821A1821B1822A1822B1823A1823B1842A1842B1825A1825B1826A1826B1827A1827B1828A1828B1829A1829B1830A1830B1831A1811B1832A1832B1833A1833B1834A1834B1835A1835B1836A1836B1837A1837B1838A1838B1839A1839B1840A1840B1841A1841B1842A1842B1843A1843B1844A1844B1845A1845B1846A1846B1847A1847B1848A1848B1849A1849B1850A1850B1851A1851B1852A1852B1853A1853B1854A1854B1855A1855B1856A1856B1857A1857B1858A1858B1859A1859B1860A1860B1861A1861B1862A1862B1863A1863B1864A1864B1865A1865B1866A1866B1867A1867B1868A1868B1869A1869B1870A1870B1871A1871B1872A1872B1873A1873B1874A1875B1875A1875B1876A1876B1877A1877B1878A1878B1879A1879B1880A1880B1881A1881B1882A1882B1883A1883B1884A1884B1885A1885B1886A1886B1887A1887B1888A1888B1889A1889B1890A1890B1891A1891B1892A1892B EXAMPLE TABLE 26Substituted 4-[3-{(5-Heteroaryl or 5-heterocyclic)-4-fluorophenyl}-acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1893A1893B1894A1894B1895A1895B1896A1896B1897A18972B1898A1898B1899A1899B1900A1900B1901A1901B1902A1902B1903A1903B1904A1904B1905A1905B1906A1906B1907A1907B1908A1908B1909A1909B1910A1910B1911A1911B1912A1912B1913A1913B1914A1914B1915A1915B1916A1916B1917A1917B1918A1918B1919A1919B1920A1920B1921A1921B1922A1922B1923A1923B1924A1924B1925A1925B1926A1926B1927A1927B1928A1928B1929A1929B1930A1930B1931A1931B1932A1932B1933A1933B1934A1934B1935A1935B1936A1936B1937A1937B1938A1938B1939A1939B1940A1940B1941A1941B1942A1942B1943A1943B1944A1944B1945A1945B1946A1946B1947A1947B1948A1948B1949A1949B1950A1950B1951A1951B1952A1952B1953A1953B1954A1954B1955A1955B EXAMPLE TABLE 27Substituted 4-[3-{(3-Heteroaryl or 3-heterocyclic)-4-(pyrrolidin-1-yl)-phenyl}acryloyl]-benzoic Acids.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β1956A1956B1957A1957B1958A1958B1959A1959B1960A1960B1961A1961B1962A1962B1963A1963B1964A1964B1965A1965B1966A1966B1967A1967B1968A1968B1969A1969B1970A1970B1971A1971B1972A1972B1973A1973B1974A1974B1975A1975B1976A1976B1977A1977B1978A1978B1979A1979B1980A1980B1981A1981B1982A1982B1983A1983B1984A1984B1985A1985B1986A1986B1987A1987B1988A1988B1989A1989B1990A1990B1991A1991B1992A1992B1993A1993B1994A1994B1995A1995B1996A1996B1997A1997B1998A1998B1999A1999B2000A2000B2001A2001B2002A2002B2003A2003B2004A2004B2005A2005B20062006B2007A2007B2008A2008B2009A2009B2010A2010B2011A2011B2012A2012B2013A2013B2014A2014B2015A2015B2016A2016B2017A2017B2018A2018B2019A2019B2020A2020B2021A2021B2022A2022B2023A2023B2024A2024B2025A2025B2026A2026B2027A2027B EXAMPLE TABLE 28Substituted 4-[3-{(5-Heteroaryl or 5-heterocyclic)-2,4-dimethoxyphenyl}-acryloyl]benzonitriles.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β2028A2028B2029A2029B2030A2030B2031A2031B2032A2032B2033A2033B2034A2034B2035A2035B2036A2036B2037A2037B2038A2038B2039A2039B2040A2040B2041A2041B2042A2042B2043A2043B2044A2044B2045A2045B2046A2046B2047A2047B2048A2048B2049A2049B2050A2050B2051A2051B2052A2052B2053A2053B2054A2054B2055A2055B2056A2056B2057A2057B2058A2058B2059A2059B2060A2060B2061A2061B2062A2062B2063A2063B2064A2064B2065A2065B2066A2066B2067A2067B2068A2068B2069A2069B2070A2070B2071A2071B2072A2072B2073A2073B2074A2074B2075A2075B2076A2076B2077A2077B2078A2078B2079A2079B2080A2080B2081A2081B2082A2082B2083A2083B2084A2084B2085A2085B2086A2086B2087A2087B2088A20881B2089A2089B2090A2090B EXAMPLE TABLE 29Substituted 3-[2,4-Dimethoxy-(5-heteroaryl or 5-heterocyclic)phenyl]-1-[4-(2H-tetrazol-5-yl)phenyl]-2-propen-1-ones.ABEx. No.R 5βEx. No.R 5βEx. No.R 5β2091A2091B2092A2092B2093A2093B2094A2094B2095A2095B2096A2096B2097A2097B2098A2098B2099A2099B2100A2100B2101A2101B2102A2102B2103A2103B2104A2104B2105A2105B2106A2106B2107A2107B2108A2108B2109A2109B2110A2110B2111A2111B2112A2112B2113A2113B2114A2114B2115A2115B2116A2116B2117A2117B2118A2118B2119A2119B2120A2120B2121A2121B2122A2122B2123A2123B2124A2124B2125A2125B2126A2126B2127A2127B2128A2128B2129A2129B2130A2130B2131A2131B2132A2132B2133A2133B2134A2134B2135A2135B2136A2136B2137A2137B2138A2138B2139A2139B2140A2130B2141A2141B2142A2142B2143A2143B2144A2145B2145A2145B2146A2146B2147A2147B2148A2148B2149A2149B2150A2150B2151A2151B2152A2152B2153A2153B2154A2154B2155A2155B2156A2156B2157A2157B2158A2158B2159A2159B2160A2160B2161A2161B2162A2162B EXAMPLE TABLE 30Substituted 4-[3-{(4-Heteroaryl or 4-heterocyclic)phenyl}-acryloyl]-benzoic Acids.ABEx. No.R 4βEx. No.R 4βEx. No.R 4β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ubstituted 4-[3-{(4-Heteroaryl or 4-heterocyclic)phenyl}-3-oxo-propenyl]-benzoic Acids.Ex. No.R 4αEx. No.R 4αEx. No.R 4α2226A2226B2227A2227B2228A2228B2229A2229B2230A2230B2231A2231B2232A2232B2233A2233B2234A2234B2235A2235B2236A2236B2237A2237B2238A2238B2239A2239B2240A2240B2241A2241B2242A2242B2243A2243B2244A2244B2245A2245B2246A2246B2247A2247B2248A2248B2249A2249B2250A2250B2251A2251B2252A2252B2253A2253B2254A2254B2255A2255B2256A2256B2257A2257B2258A2258B2259A2259B2260A2260B2261A2261B2262A2262B2263A2263B2264A2264B2265A2265B2266A2266B2267A2267B2268A2268B2269A2269B2270A2270B2271A2271B2272A2272B2273A2273B2274A2274B2275A2275B2276A2276B2277A2277B2278A2278B2279A2279B2280A2280B2281A2281B2282A2282B2283A2283B2284A2284B2285A2285B2286A2286B2287A2287B2288A2288B2289A2289B2290A2290B2291A2291B2292A2292B2293A2293B2294A2294B2295A2295B2296A2296B2297A2297B EXAMPLE TABLE 32Substituted 4-[3-{(4-Heteroaryl or 4-heterocyclic)-2,6-dimethoxyphenyl}-acryloyl]-benzoic Acids.Ex. No.R 4βEx. No.R 4βEx. No.R 4β2298A2298B2299A2299B2300A2300B2301A2301B2302A2302B2303A2303B2304A2304B2305A2305B2306A2306B2307A2307B2308A2308B2309A2309B2310A2310B2311A2311B2312A2312B2313A2313B2314A2314B2315A2315B2316A2316B2317A2317B2318A2318B2319A2319B2320A2320B2321A2321B2322A2322B2323A2323B2324A2324B2325A2325B2326A2326B2327A2327B2328A2328B2329A2329B2330A2330B2331A2331B2332A2332B2333A2333B2334A2334B2335A2335B2336A2336B2337A2337B2338A2338B2339A2339B2340A2340B2341A2341B2342A2342B2343A2343B2344A2344B2345A2345B2346A2346B2347A2347B2348A2348B2349A2349B2350A2350B2351A2351B2352A2352B2353A2353B2354A2354B2355A2355B2356A2356B2357A2357B2358A2358B2359A2359B2360A2360B EXAMPLE TABLE 33Substituted 4-[3-{(5-Heteroaryl or 5-heterocyclic)-2,4-dimethoxyphenyl}-acryloyl]-benzoic Acids.Ex. No.R 5βEx. No.R 5βEx. No.R 5β2361A2361B2362A2362B2363A2363B2364A2364B2365A2365B2366A2366B2367A2367B2368A2368B2369A2369B Stereoisomerism and Polymorphism It is appreciated that compounds of the present invention having a chiral center may exist in and be isolated in optically active and racemic forms. Some compounds may exhibit polymorphism. It is to be understood that the present invention encompasses any racemic, optically-active, diastereomeric, polymorphic, or stereoisomeric form, or mixtures thereof, of a compound of the invention, which possess the useful properties described herein, it being well known in the art how to prepare optically active forms (for example, by resolution of the racemic form by recrystallization techniques, by synthesis from optically-active starting materials, by chiral synthesis, or by chromatographic separation using a chiral stationary phase). Examples of methods to obtain optically active materials are known in the art, and include at least the following. i) physical separation of crystals—a technique whereby macroscopic crystals of the individual enantiomers are manually separated. This technique can be used if crystals of the separate enantiomers exist, i.e., the material is a conglomerate, and the crystals are visually distinct;ii) simultaneous crystallization—a technique whereby the individual enantiomers are separately crystallized from a solution of the racemate, possible only if the latter is a conglomerate in the solid state;iii) enzymatic resolutions—a technique whereby partial or complete separation of a racemate by virtue of differing rates of reaction for the enantiomers with an enzyme;iv) enzymatic asymmetric synthesis—a synthetic technique whereby at least one step of the synthesis uses an enzymatic reaction to obtain an enantiomerically pure or enriched synthetic precursor of the desired enantiomer;v) chemical asymmetric synthesis—a synthetic technique whereby the desired enantiomer is synthesized from an achiral precursor under conditions that produce asymmetry (i.e., chirality) in the product, which may be achieved using chiral catalysts or chiral auxiliaries;vi) diastereomer separations—a technique whereby a racemic compound is reacted with an enantiomerically pure reagent (the chiral auxiliary) that converts the individual enantiomers to diastereomers. The resulting diastereomers are then separated by chromatography or crystallization by virtue of their now more distinct structural differences and the chiral auxiliary later removed to obtain the desired enantiomer;vii) first- and second-order asymmetric transformations—a technique whereby diastereomers from the racemate equilibrate to yield a preponderance in solution of the diastereomer from the desired enantiomer or where preferential crystallization of the diastereomer from the desired enantiomer perturbs the equilibrium such that eventually in principle all the material is converted to the crystalline diastereomer from the desired enantiomer. The desired enantiomer is then released from the diastereomer;viii) kinetic resolutions—this technique refers to the achievement of partial or complete resolution of a racemate (or of a further resolution of a partially resolved compound) by virtue of unequal reaction rates of the enantiomers with a chiral, non-racemic reagent or catalyst under kinetic conditions;ix) enantiospecific synthesis from non-racemic precursors—a synthetic technique whereby the desired enantiomer is obtained from non-chiral starting materials and where the stereochemical integrity is not or is only minimally compromised over the course of the synthesis;x) chiral liquid chromatography—a technique whereby the enantiomers of a racemate are separated in a liquid mobile phase by virtue of their differing interactions with a stationary phase. The stationary phase can be made of chiral material or the mobile phase can contain an additional chiral material to provoke the differing interactions;xi) chiral gas chromatography—a technique whereby the racemate is volatilized and enantiomers are separated by virtue of their differing interactions in the gaseous mobile phase with a column containing a fixed non-racemic chiral adsorbent phase;xii) extraction with chiral solvents—a technique whereby the enantiomers are separated by virtue of preferential dissolution of one enantiomer into a particular chiral solvent;xiii) transport across chiral membranes—a technique whereby a racemate is placed in contact with a thin membrane barrier. The barrier typically separates two miscible fluids, one containing the racemate, and a driving force such as concentration or pressure differential causes preferential transport across the membrane barrier. Separation occurs as a result of the non-racemic chiral nature of the membrane which allows only one enantiomer of the racemate to pass through. Pharmaceutically Acceptable Salt Formulations In cases where compounds are sufficiently basic or acidic to form stable nontoxic acid or base salts, administration of the compound as a pharmaceutically acceptable salt may be appropriate. The term “pharmaceutically acceptable salts” or “complexes” refers to salts or complexes that retain the desired biological activity of the compounds of the present invention and exhibit minimal undesired toxicological effects. Examples of pharmaceutically acceptable salts are organic acid addition salts formed with acids, which form a physiological acceptable anion, for example, tosylate, methanesulfonate, acetate, citrate, malonate, tartarate, succinate, benzoate, ascorbate, α-ketoglutarate and α-glycerophosphate. Suitable inorganic salts may also be formed, including, sulfate, nitrate, bicarbonate and carbonate salts. Alternatively, the pharmaceutically acceptable salts may be made with sufficiently basic compounds such as an amine with a suitable acid affording a physiologically acceptable anion. Alkali metal (for example, sodium, potassium or lithium) or alkaline earth metal (for example calcium) salts of carboxylic acids can also be made. Nonlimiting examples of such salts are (a) acid addition salts formed with inorganic acids (for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, and the like), and salts formed with organic acids such as acetic acid, oxalic acid, tartaric acid, succinic acid, malic acid, ascorbic acid, benzoic acid, tannic acid, pamoic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, naphthalenedisulfonic acid, and polygalcturonic acid; (b) base addition salts formed with metal cations such as zinc, calcium, bismuth, barium, magnesium, aluminum, copper, cobalt, nickel, cadmium, sodium, potassium, and the like, or with a cation formed from ammonia, N,N-dibenzylethylenediamine, D-glucosamine, tetraethylammonium, or ethylenediamine; or (c) combinations of (a) and (b); e.g., a zinc tannate salt or the like. Also included in this definition are pharmaceutically acceptable quaternary salts known by those skilled in the art, which specifically include the quaternary ammonium salt of the formula —NR + A − , wherein R is as defined above and A is a counterion, including chloride, bromide, iodide, —O-alkyl, toluenesulfonate, methylsulfonate, sulfonate, phosphate, or carboxylate (such as benzoate, succinate, acetate, glycolate, maleate, malate, citrate, tartrate, ascorbate, benzoate, cinnamoate, mandeloate, benzyloate, and diphenylacetate). Particular FDA-approved salts can be conveniently divided between anions and cations (Approved Drug Products with Therapeutic Equivalence Evaluations (1994) U.S. Department of Health and Human Services, Public Health Service, FDA, Center for Drug Evaluation and Research, Rockville, Md.; L. D. Bighley, S. M. Berge and D. C. Monkhouse, Salt Forms of Drugs and Absorption, Encyclopedia of Pharmaceutical Technology , Vol. 13, J. Swarbridk and J. Boylan, eds., Marcel Dekker, NY (1996)). Among the approved anions include aceglumate, acephyllinate, acetamidobenzoate, acetate, acetylasparaginate, acetylaspartate, adipate, aminosalicylate, anhydromethylenecitrate, ascorbate, aspartate, benzoate, besylate, bicarbonate, bisulfate, bitartrate, borate, bromide, camphorate, camsylate, carbonate, chloride, chlorophenoxyacetate, citrate,closylate, cromesilate, cyclamate, dehydrocholate, dihydrochloride, dimalonate, edentate, edisylate, estolate, esylate, ethylbromide, ethylsulfate, fendizoate, fosfatex, fumarate, gluceptate, gluconate, glucuronate, glutamate, glycerophosphate, glysinate, glycollylarsinilate, glycyrrhizate, hippurate, hemisulfate, hexylresorcinate, hybenzate, hydrobromide, hydrochloride, hydroiodid, hydroxybenzenesulfonate, hydroxybenzoate, hydroxynaphthoate, hyclate, iodide, isethionate, lactate, lactobionate, lysine, malate, maleate, mesylate, methylbromide, methyliodide, methylnitrate, methylsulfate, monophosadenine, mucate, napadisylate, napsylate, nicotinate, nitrate, oleate, orotate, oxalate, oxoglurate, pamoate, pantothenate, pectinate, phenylethylbarbiturate, phosphate, pacrate, plicrilix, polistirex, polygalacturonate, propionate, pyridoxylphosphate, saccharinate, salicylate, stearate, succinate, stearylsulfate, subacetate, succinate, sulfate, sulfosalicylate, tannate, tartrate, teprosilate, terephthalate, teoclate, thiocyante, tidiacicate, timonacicate, tosylate, triethiodide, triethiodide, undecanoate, and xinafoate. The approved cations include ammonium, benethamine, benzathine, betaine, calcium, carnitine, clemizole, chlorcyclizine, choline, dibenylamine, diethanolamine, diethylamine, diethylammonium diolamine, eglumine, erbumine, ethylenediamine, heptaminol, hydrabamine, hydroxyethylpyrrolidone, imadazole, meglumine, olamine, piperazine, 4-phenylcyclohexylamine, procaine, pyridoxine, triethanolamine, and tromethamine. Metallic cations include, aluminum, bismuth, calcium lithium, magnesium, neodymium, potassium, rubidium, sodium, strontium and zinc. A particular class of salts can be classified as organic amine salts. The organic amines used to form these salts can be primary amines, secondary amines or tertiary amines, and the substituents on the amine can be straight, branched or cyclic groups, including ringed structures formed by attachment of two or more of the amine substituents. Of particular interest are organic amines that are substituted by one or more hydroxyalkyl groups, including alditol or carbohydrate moieties. These hydroxy substituted organic amines can be cyclic or acyclic, both classes of which can be primary amines, secondary amines or tertiary amines. A common class of cyclic hydroxy substituted amines are the amino sugars. Carbohydrate moieties that can comprise one or more substituents in the amine salt include those made from substituted and unsubstituted monosaccharides, disaccharides, oligosaccharides, and polysaccharides. The saccharide can be an aldose or ketose, and may comprise 3, 4, 5, 6, or 7 carbons. In one embodiment the carbohydrates are monosaccharides. In another embodiment the carbohydrates are pyranose and furanose sugars. Non limiting examples of pyranose and furanose moieties that can be part of the organic amine salt include threose, ribulose, ketose, gentiobiose, aldose, aldotetrose, aldopentose, aldohexose, ketohexose, ketotetrose, ketopentose, erythrose, threose, ribose, deoxyribose, arabinose, xylose, lyxose, allose, altrose, glucose, mannose, gulose, idose, glactose, talose, erythrulose, ribulose, xylulose, psicose, fructose, sorbose, tagatose, dextrose, maltose, lactose, sucrose, cellulose, aldose, amylose, palatinose, trehalose, turanose, cellobiose, amylopectin, glucosamine, mannosamine, fucose, phamnose, glucuronate, gluconate, glucono-lactone, muramic acid, abequose, rhamnose, gluconic acid, glucuronic acid, and galactosamine. The carbohydrate moiety can optionally be deoxygenated at any corresponding C-position, and/or substituted with one or more moieties such as hydrogen, halo, haloalkyl, carboxyl, acyl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, thioester, thioether, oxime, hydrazine, carbamate, phosphonic acid, phosphonate, or any other viable functional group that does not inhibit the pharmacological activity of this compound. Exemplary substituents include amine and halo, particularly fluorine. The substituent or carbohydrate can be either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene, et al., Protective Groups in Organic Synthesis , John Wiley and Sons, Second Edition, 1991, hereby incorporated by reference. In one embodiment the monosaccharide is a furanose such as (L or D)-ribose. Of particular interest among the acyclic organic amines are a class represented by the formula wherein Y and Z are independently hydrogen or lower alkyl or, may be taken together to form a ring, R is hydrogen, alkyl or hydroxyloweralkyl, and n is 1, 2, 3, 4, or 5. Among these hydroxyl amines are a particular class characterized when n is 4. A representative of this group is meglumine, represented when Y is hydrogen, Z is methyl and R is methoxy. Meglumine is also known in the art as N-methylglucamine, N-MG, and 1-deoxy-1-(methylamino)-D-glucitol. The invention also includes pharmaceutically acceptable prodrugs of the compounds. Pharmaceutically acceptable prodrugs refer to a compound that is metabolized, for example hydrolyzed or oxidized, in the host to form the compound of the present invention. Typical examples of prodrugs include compounds that have biologically labile protecting groups on a functional moiety of the active compound. Prodrugs include compounds that can be oxidized, reduced, aminated, deaminated, hydroxylated, dehydroxylated, hydrolyzed, dehydrolyzed, alkylated, dealkylated, acylated, deacylated, phosphorylated, dephosphorylated to produce the active compound. Any of the compounds described herein can be administered as a prodrug to increase the activity, bioavailability, stability or otherwise alter the properties of the compound. A number of prodrug ligands are known. In general, alkylation, acylation or other lipophilic modification of the compound will increase the stability of the chalcone. Examples of substituent groups that can replace one or more hydrogens on the compound are alkyl, aryl, steroids, carbohydrates, including sugars, 1,2-diacylglycerol and alcohols. Many are described in R. Jones and N. Bischofberger, Antiviral Research, 27 (1995) 1–17. Any of these can be used in combination with the disclosed compounds to achieve a desired effect. The compounds can be used to treat inflammatory disorders that are mediated by VCAM-1 including, but not limited to arthritis, asthma, dermatitis, psoriasis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, diabetic nephropathy, diabetic vasculopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. The compounds disclosed herein can be used in the treatment of inflammatory skin diseases that are mediated by VCAM-1, and in particular, human endothelial disorders that are mediated by VCAM-1, which include, but are not limited to, psoriasis, dermatitis, including eczematous dermatitis, and Kaposi's sarcoma, as well as proliferative disorders of smooth muscle cells. In yet another embodiment, the compounds disclosed herein can be selected to treat anti-inflammatory conditions that are mediated by mononuclear leucocytes. In yet another embodiment, the compounds of the present invention can be selected for the prevention or treatment of tissue or organ transplant rejection. Treatment and prevention of organ or tissue transplant rejection includes, but are not limited to treatment of recipients of heart, lung, combined heart-lung, liver, kidney, pancreatic, skin, spleen, small bowel, or corneal transplants. They are also indicated for the prevention or treatment of graft-versus-host disease, which sometimes occurs following bone marrow transplantation. In an alternative embodiment, the compounds described herein are useful in both the primary and adjunctive medical treatment of cardiovascular disease. The compounds are used in primary treatment of, for example, coronary disease states including atherosclerosis, post-angioplasty restenosis, coronary artery diseases and angina. The compounds can be administered to treat small vessel disease that is not treatable by surgery or angioplasty, or other vessel disease in which surgery is not an option. The compounds can also be used to stabilize patients prior to revascularization therapy. In another aspect the invention provides pharmaceutical compositions for the treatment of diseases or disorders mediated by VCAM-1 wherein such compositions comprise a VCAM-1 inhibiting amount of a chalcone derivatives of the invention or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable carrier. In another aspect the invention provides a method for treating a disease or disorder mediated by VCAM-1 comprising administering to a patient a VCAM-1 inhibiting effective amount of a compound of the invention or a pharmaceutically acceptable salt thereof. In another aspect the invention provides a method for treating cardiovascular and inflammatory disorders in a patient in need thereof comprising administering to said patient an VCAM-1 inhibiting effective amount of a compound of the invention or a pharmaceutically acceptable salt thereof. In another aspect the invention provides a method and composition for treating asthma or arthritis in a patient in need thereof comprising administering to said patient an effective amount of a compound of the invention or a pharmaceutically acceptable salt thereof. The compounds of the present invention can be used to treat any disorder that is mediated by VCAM-1. VCAM-1 is upregulated in a wide variety of disease states, including but not limited to arthritis, asthma, dermatitis, psoriasis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, diabetic nephropathy, diabetic vasculopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, atherosclerosis, coronary artery disease, angina, small artery disease, and conjunctivitis. Nonlimiting examples of arthritis include rheumatoid (such as soft-tissue rheumatism and non-articular rheumatism, fibromyalgia, fibrositis, muscular rheumatism, myofascil pain, humeral epicondylitis, frozen shoulder, Tietze's syndrome, fascitis, tendinitis, tenosynovitis, bursitis), juvenile chronic, spondyloarthropaties (ankylosing spondylitis), osteoarthritis, hyperuricemia and arthritis associated with acute gout, chronic gout and systemic lupus erythematosus. Human endothelial disorders mediated by VCAM-1 include psoriasis, eczematous dermatitis, Kaposi's sarcoma, as well as proliferative disorders of smooth muscle cells. In yet another embodiment, the compounds disclosed herein can be selected to treat anti-inflammatory conditions that are mediated by mononuclear leucocytes. In one embodiment, the compounds of the present invention are selected for the prevention or treatment of tissue or organ transplant rejection. Treatment and prevention of organ or tissue transplant rejection includes, but are not limited to treatment of recipients of heart, lung, combined heart-lung, liver, kidney, pancreatic, skin, spleen, small bowel, or corneal transplants. The compounds can also be used in the prevention or treatment of graft-versus-host disease, such as sometimes occurs following bone marrow transplantation. In an alternative embodiment, the compounds described herein are useful in both the primary and adjunctive medical treatment of cardiovascular disease. The compounds are used in primary treatment of, for example, coronary disease states including atherosclerosis, post-angioplasty restenosis, coronary artery diseases and angina. The compounds can be administered to treat small vessel disease that is not treatable by surgery or angioplasty, or other vessel disease in which surgery is not an option. The compounds can also be used to stabilize patients prior to revascularization therapy. In addition to inhibiting the expression of VCAM-1, some of the compounds of the invention have the additional properties of inhibiting monocyte chemoattractant protein-1 (MCP-1) and/or smooth muscle proliferation. MCP-1 is a chemoattractant protein produced by endothelial cells, smooth muscle cells as well as macrophages. MCP-1 promotes integrin activation on endothelial cells thereby facilitating adhesion of leukocytes to VCAM-1, and MCP-1 is a chemoattractant for monocytes. MCP-1 has been shown to play a role in leukocyte recruitment in a number of chronic inflammatory diseases including atherosclerosis, rheumatoid arthritis, and asthma. Its expression is upregulated in these diseases and as such inhibition of MCP-1 expression represents a desirable property of anti-inflammatory therapeutics. Furthermore, smooth muscle cell hyperplasia and resulting tissue remodeling and decreased organ function is yet another characteristic of many chronic inflammatory diseases including atherosclerosis, chronic transplant rejection and asthma. Inhibition of the hyperproliferation of smooth muscle cells is another desirable property for therapeutic compounds. Combination and Alternation Therapy Any of the compounds disclosed herein can be administered in combination or alternation with a second biologically active agent to increase its effectiveness against the target disorder. In combination therapy, effective dosages of two or more agents are administered together, whereas during alternation therapy an effective dosage of each agent is administered serially. The dosages will depend on absorption, inactivation and excretion rates of the drug as well as other factors known to those of skill in the art. It is to be noted that dosage values will also vary with the severity of the condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens and schedules should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions. The efficacy of a drug can be prolonged, augmented, or restored by administering the compound in combination or alternation with a second, and perhaps third, agent that induces a different biological pathway from that caused by the principle drug. Alternatively, the pharmacokinetics, biodistribution or other parameter of the drug can be altered by such combination or alternation therapy. In general, combination therapy is typically preferred over alternation therapy because it induces multiple simultaneous stresses on the condition. Any method of alternation can be used that provides treatment to the patient. Nonlimiting examples of alternation patterns include 1–6 weeks of administration of an effective amount of one agent followed by 1–6 weeks of administration of an effective amount of a second agent. The alternation schedule can include periods of no treatment. Combination therapy generally includes the simultaneous administration of an effective ratio of dosages of two or more active agents. Illustrative examples of specific agents that can be used in combination or alternation with the compounds of the present invention are described below in regard to asthma and arthritis. The agents set out below or others can alternatively be used to treat a host suffering from any of the other disorders listed above or that are mediated by VCAM-1 or MCP-1. Illustrative second biologically active agents for the treatment of cardiovascular disease are also provided below. Asthma In one embodiment, the compounds of the present invention are administered in combination or alternation with heparin, frusemide, ranitidine, an agent that effects respiratory function, such as DNAase, or immunosuppressive agents, IV gamma globulin, troleandomycin, cyclosporin (Neoral), methotrexate, FK-506, gold compounds such as Myochrysine (gold sodium thiomalate), platelet activating factor (PAF) antagonists such as thromboxane inhibitors, leukotriene-D 4 -receptor antagonists such as Accolate (zafirlukast), Ziflo (zileuton), leukotriene C 1 or C 2 antagonists and inhibitors of leukotriene synthesis such as zileuton for the treatment of asthma, or an inducible nitric oxide synthase inhibitor. In another embodiment, the active compound is administered in combination or alternation with one or more other prophylactic agent(s). Examples of prophylactic agents that can be used in alternation or combination therapy include but are not limited to sodium cromoglycate, Intal (cromolyn sodium, Nasalcrom, Opticrom, Crolom, Ophthalmic Crolom), Tilade (nedocromil, nedocromil sodium) and ketotifen. In another embodiment, the active compound is administered in combination or alternation with one or more other β 2 -adrenergic agonist(s) (β agonists). Examples of β 2 -adrenergic agonists (β agonists) that can be used in alternation or combination therapy include but are not limited to albuterol (salbutamol, Proventil, Ventolin), terbutaline, Maxair (pirbuterol), Serevent (salmeterol), epinephrine, metaproterenol (Alupent, Metaprel), Brethine (Bricanyl, Brethaire, terbutaline sulfate), Tornalate (bitolterol), isoprenaline, ipratropium bromide, bambuterol hydrochloride, bitolterol meslyate, broxaterol, carbuterol hydrochloride, clenbuterol hydrochloride, clorprenaline hydrochloride, efirmoterol fumarate, ephedra (source of alkaloids), ephedrine (ephedrine hydrochloride, ephedrine sulfate), etafedrine hydrochloride, ethylnoradrenaline hydrochloride, fenoterol hydrochloride, hexoprenaline hydrochloride, isoetharine hydrochloride, isoprenaline, mabuterol, methoxyphenamine hydrochloride, methylephedrine hydrochloride, orciprenaline sulphate, phenylephrine acid tartrate, phenylpropanolamine (phenylpropanolamine polistirex, phenylpropanolamine sulphate), pirbuterol acetate, procaterol hydrochloride, protokylol hydrochloride, psuedoephedrine (psuedoephedrine polixtirex, psuedoephedrine tannate, psuedoephedrine hydrochloride, psuedoephedrine sulphate), reproterol hydrochloride, rimiterol hydrobromide, ritodrine hydrochloride, salmeterol xinafoate, terbutaline sulphate, tretoquinol hydrate and tulobuterol hydrochloride. In another embodiment, the active compound is administered in combination or alternation with one or more other corticosteriod(s). Examples of corticosteriods that can be used in alternation or combination therapy include but are not limited to glucocorticoids (GC), Aerobid (Aerobid-M, flunisolide), Azmacort (triamcinolone acetonide), Beclovet (Vanceril, beclomethasone dipropionate), Flovent (fluticasone), Pulmicort (budesonide), prednisolone, hydrocortisone, adrenaline, Alclometasone Dipropionate, Aldosterone, Amcinonide, Beclomethasone Dipropionate, Bendacort, Betamethasone (Betamethasone Acetate, Betamethasone Benzoate, Betamethasone Dipropionate, Betamethasone Sodium Phosphate, Betamethasone Valerate), Budesonide, Ciclomethasone, Ciprocinonide, Clobetasol Propionate, Clobetasone Butyrate, Clocortolone Pivalate, Cloprednol, Cortisone Acetate, Cortivazol, Deflazacort, Deoxycortone Acetate (Deoxycortone Pivalate), Deprodone, Desonide, Desoxymethasone, Dexamethasone (Dexamethasone Acetate, Dexamethasone Isonicotinate, Dexamethasone Phosphate, Dexamethasone Sodium Metasulphobenzoate, Dexamethasone Sodium Phosphate), Dichlorisone Acetate, Diflorasone Diacetate, Diflucortolone Valerate, Difluprednate, Domoprednate, Endrysone, Fluazacort, Fluclorolone Acetonide, Fludrocortisone Acetate, Flumethasone (Flumethasone Pivalate), Flunisolide, Fluocinolone Acetonide, Fluocinonide, Fluocortin Butyl, Fluocortolone (Fluocortolone Hexanoate, Fluocortolone Pivalate), Fluorometholone (Fluorometholone Acetate), Fluprednidene Acetate, Fluprednisolone, Flurandrenolone, Fluticasone Propionate, Formocortal, Halcinonide, Halobetasol Propionate, Halometasone, Hydrocortamate Hydrochloride, Hydrocortisone (Hydrocortisone Acetate, Hydrocortisone Butyrate, Hydrocortisone Cypionate, Hydrocortisone Hemisuccinate, Hydrocortisone Sodium Phosphate, Hydrocortisone Sodium Succinate, Hydrocortisone Valerate), Medrysone, Meprednisone, Methylprednisolone (Methylprednisolone Acetate, Methylprednisolone, Hemisuccinate, Methylprednisolone Sodium Succinate), Mometasone Furoate, Paramethasone Acetate, Prednicarbate, Prednisolamate Hydrochloride, Prednisolone (Prednisolone Acetate, Prednisolone Hemisuccinate, Prednisolone Hexanoate, Prednisolone Pivalate, Prednisolone Sodium Metasulphobenzoate, Prednisolone Sodium Phosphate, Prednisolone Sodium Succinate, Prednisolone Steaglate, Prednisolone Tebutate), Prednisone (Prednisone Acetate), Prednylidene, Procinonide, Rimexolone, Suprarenal Cortex, Tixocortol Pivalate, Triamcinolone (Triamcinolone Acetonide, Triamcinolone Diacetate and Triamcinolone Hexacetonide). In another embodiment, the active compound is administered in combination or alternation with one or more other antihistimine(s) (H 1 receptor antagonists). Examples of antihistimines (H 1 receptor antagonists) that can be used in alternation or combination therapy include alkylamines, ethanolamines ethylenediamines, piperazines, piperidines or phenothiazines. Some non-limiting examples of antihistimes are Chlortrimeton (Teldrin, chlorpheniramine), Atrohist (brompheniramine, Bromarest, Bromfed, Dimetane), Actidil (triprolidine), Dexchlor (Poladex, Polaramine, dexchlorpheniramine), Benadryl (diphen-hydramine), Tavist (clemastine), Dimetabs (dimenhydrinate, Dramamine, Marmine), PBZ (tripelennamine), pyrilamine, Marezine (cyclizine), Zyrtec (cetirizine), hydroxyzine, Antivert (meclizine, Bonine), Allegra (fexofenadine), Hismanal (astemizole), Claritin (loratadine), Seldane (terfenadine), Periactin (cyproheptadine), Nolamine (phenindamine, Nolahist), Phenameth (promethazine, Phenergan), Tacaryl (methdilazine) and Temaril (trimeprazine). Alternatively, the compound of the present invention is administered in combination or alternation with (a) xanthines and methylxanthines, such as Theo-24 (theophylline, Slo-Phylline, Uniphyllin, Slobid, Theo-Dur), Choledyl (oxitriphylline), aminophylline;(b) anticholinergic agents (antimuscarinic agents) such as belladonna alkaloids, Atrovent (ipratropium bromide), atropine, oxitropium bromide;(c) phosphodiesterase inhibitors such as zardaverine;(d) calcium antagonists such as nifedipine; or(e) potassium activators such as cromakalim for the treatment of asthma. Arthritic Disorders In one embodiment, the compound of the present invention can also be administered in combination or alternation with apazone, amitriptyline, chymopapain, collegenase, cyclobenzaprine, diazepam, fluoxetine, pyridoxinee, ademetionine, diacerein, glucosamine, hylan (hyaluronate), misoprostol, paracetamol, superoxide dismutase mimics, TNFα receptor antagonists, TNFα antibodies, P38 Kinase inhibitors, tricyclic antidepressents, cJun kinase inhibitors or immunosuppressive agents, IV gamma globulin, troleandomycin, cyclosporin (Neoral), methotrexate, FK-506, gold compounds such as Myochrysine (gold sodium thiomalate), platelet activating factor (PAF) antagonists such as thromboxane inhibitors, and inducible nitric oxide sythase inhibitors. In another embodiment, the active compound is administered in combination or alternation with one or more other corticosteriod(s). Examples of corticosteriods that can be used in alternation or combination therapy include but are not limited to glucocorticoids (GC), Aerobid (Aerobid-M, flunisolide), Azmacort (triamcinolone acetonide), Beclovet (Vanceril, beclomethasone dipropionate), Flovent (fluticasone), Pulmicort (budesonide), prednisolone, hydrocortisone, adrenaline, Alclometasone Dipropionate, Aldosterone, Amcinonide, Beclomethasone Dipropionate, Bendacort, Betamethasone (Betamethasone Acetate, Betamethasone Benzoate, Betamethasone Dipropionate, Betamethasone Sodium Phosphate, Betamethasone Valerate), Budesonide, Ciclomethasone, Ciprocinonide, Clobetasol Propionate, Clobetasone Butyrate, Clocortolone Pivalate, Cloprednol, Cortisone Acetate, Cortivazol, Deflazacort, Deoxycortone Acetate (Deoxycortone Pivalate), Deprodone, Desonide, Desoxymethasone, Dexamethasone (Dexamethasone Acetate, Dexamethasone Isonicotinate, Dexamethasone Phosphate, Dexamethasone Sodium Metasulphobenzoate, Dexamethasone Sodium Phosphate), Dichlorisone Acetate, Diflorasone Diacetate, Diflucortolone Valerate, Difluprednate, Domoprednate, Endrysone, Fluazacort, Fluclorolone Acetonide, Fludrocortisone Acetate, Flumethasone (Flumethasone Pivalate), Flunisolide, Fluocinolone Acetonide, Fluocinonide, Fluocortin Butyl, Fluocortolone (Fluocortolone Hexanoate, Fluocortolone Pivalate), Fluorometholone (Fluorometholone Acetate), Fluprednidene Acetate, Fluprednisolone, Flurandrenolone, Fluticasone Propionate, Formocortal, Halcinonide, Halobetasol Propionate, Halometasone, Hydrocortamate Hydrochloride, Hydrocortisone (Hydrocortisone Acetate, Hydrocortisone Butyrate, Hydrocortisone Cypionate, Hydrocortisone Hemisuccinate, Hydrocortisone Sodium Phosphate, Hydrocortisone Sodium Succinate, Hydrocortisone Valerate), Medrysone, Meprednisone, Methylprednisolone (Methylprednisolone Acetate, Methylprednisolone, Hemisuccinate, Methylprednisolone Sodium Succinate), Mometasone Furoate, Paramethasone Acetate, Prednicarbate, Prednisolamate Hydrochloride, Prednisolone (Prednisolone Acetate, Prednisolone Hemisuccinate, Prednisolone Hexanoate, Prednisolone Pivalate, Prednisolone Sodium Metasulphobenzoate, Prednisolone Sodium Phosphate, Prednisolone Sodium Succinate, Prednisolone Steaglate, Prednisolone Tebutate), Prednisone (Prednisone Acetate), Prednylidene, Procinonide, Rimexolone, Suprarenal Cortex, Tixocortol Pivalate, Triamcinolone (Triamcinolone Acetonide, Triamcinolone Diacetate and Triamcinolone Hexacetonide). In another embodiment, the active compound is administered in combination or alternation with one or more other non-steroidal anti-inflammatory drug(s) (NSAIDS). Examples of NSAIDS that can be used in alternation or combination therapy are carboxylic acids, propionic acids, fenamates, acetic acids, pyrazolones, oxicans, alkanones, gold compounds and others that inhibit prostaglandin synthesis, preferably by selectively inhibiting cylcooxygenase-2 (COX-2). Some nonlimiting examples of COX-2 inhibitors are Celebrex (celecoxib), Bextra (valdecoxib), Dynastat (parecoxib sodium) and Vioxx (rofacoxib). Some non-limiting examples of NSAIDS are aspirin (acetylsalicylic acid), Dolobid (diflunisal), Disalcid (salsalate, salicylsalicylate), Trisilate (choline magnesium trisalicylate), sodium salicylate, Cuprimine (penicillamine), Tolectin (tolmetin), ibuprofen (Motrin, Advil, Nuprin Rufen), Naprosyn (naproxen, Anaprox, naproxen sodium), Nalfon (fenoprofen), Orudis (ketoprofen), Ansaid (flurbiprofen), Daypro (oxaprozin), meclofenamate (meclofanamic acid, Meclomen), mefenamic acid, Indocin (indomethacin), Clinoril (sulindac), tolmetin, Voltaren (diclofenac), Lodine (etodolac), ketorolac, Butazolidin (phenylbutazone), Tandearil (oxyphenbutazone), piroxicam (Feldene), Relafen (nabumetone), Myochrysine (gold sodium thiomalate), Ridaura (auranofin), Solganal (aurothioglucose), acetaminophen, colchicine, Zyloprim (allopurinol), Benemid (probenecid), Anturane (sufinpyrizone), Plaquenil (hydroxychloroquine), Aceclofenac, Acemetacin, Acetanilide, Actarit, Alclofenac, Alminoprofen, Aloxiprin, Aluminium Aspirin, Amfenac Sodium, Amidopyrine, Aminopropylone, Ammonium Salicylate, Ampiroxicam, Amyl Salicylate, Anirolac, Aspirin, Auranofin, Aurothioglucose, Aurotioprol, Azapropazone, Bendazac (Bendazac Lysine), Benorylate, Benoxaprofen, Benzpiperylone, Benzydamine, Hydrochloride, Bornyl Salicylate, Bromfenac Sodium, Bufexamac, Bumadizone Calcium, Butibufen Sodium, Capsaicin, Carbaspirin Calcium, Carprofen, Chlorthenoxazin, Choline Magnesium Trisalicylate, Choline Salicylate, Cinmetacin, Clofexamide, Clofezone, Clometacin, Clonixin, Cloracetadol, Cymene, Diacerein, Diclofenac (Diclofenac Diethylammonium Salt, Diclofenac Potassium, Diclofenac Sodium), Diethylamine Salicylate, Diethylsalicylamide, Difenpiramide, Diflunisal, Dipyrone, Droxicam, Epirizole, Etenzamide, Etersalate, Ethyl Salicylate, Etodolac, Etofenamate, Felbinac, Fenbufen, Fenclofenac, Fenoprofen Calcium, Fentiazac, Fepradinol, Feprazone, Floctafenine, Flufenamic, Flunoxaprofen, Flurbiprofen (Flurbiprofen Sodium), Fosfosal, Furprofen, Glafenine, Glucametacin, Glycol Salicylate, Gold Keratinate, Harpagophytum Procumbens, Ibufenac, Ibuprofen, Ibuproxam, Imidazole Salicylate, Indomethacin (Indomethacin Sodium), Indoprofen, Isamifazone, Isonixin, Isoxicam, Kebuzone, Ketoprofen, Ketorolac Trometamol, Lithium Salicylate, Lonazolac Calcium, Lomoxicam, Loxoprofen Sodium, Lysine Aspirin, Magnesium Salicylate, Meclofenamae Sodium, Mefenamic Acid, Meloxicam, Methyl Butetisalicylate, Methyl Gentisate, Methyl Salicylate, Metiazinic Acid, Metifenazone, Mofebutazone, Mofezolac, Morazone Hydrochloride, Morniflumate, Morpholine Salicylate, Nabumetone, Naproxen (Naproxen Sodium), Nifenazone, Niflumic Acid, Nimesulide, Oxametacin, Oxaprozin, Oxindanac, Oxyphenbutazone, Parsalmide, Phenybutazone, Phenyramidol Hydrochloride, Picenadol Hydrochloride, Picolamine Salicylate, Piketoprofen, Pirazolac, Piroxicam, Pirprofen, Pranoprofen, Pranosal, Proglumetacin Maleate, Proquazone, Protizinic Acid, Ramifenazone, Salacetamide, Salamidacetic Acid, Salicylamide, Salix, Salol, Salsalate, Sodium Aurothiomalate, Sodium Gentisate, Sodium Salicylate, Sodium Thiosalicylate, Sulindac, Superoxide Dismutase (Orgotein, Pegorgotein, Sudismase), Suprofen, Suxibuzone, Tenidap Sodium, Tenoxicam, Tetrydamine, Thurfyl Salicylate, Tiaprofenic, Tiaramide Hydrochloride, Tinoridine Hydrochloride, Tolfenamic Acid, Tometin Sodium, Triethanolamine Salicylate, Ufenamate, Zaltoprofen, Zidometacin and Zomepirac Sodium. Cardiovascular Disease Compounds useful for combining with the compounds of the present invention for the treatment of cardiovascular disease encompass a wide range of therapeutic compounds. Ileal bile acid transporter (IBAT) inhibitors, for example, are useful in the present invention, and are disclosed in patent application no. PCT/US95/10863, herein incorporated by reference. More IBAT inhibitors are described in PCT/US97/04076, herein incorporated by reference. Still further IBAT inhibitors useful in the present invention are described in U.S. application Ser. No. 08/816,065, herein incorporated by reference. More IBAT inhibitor compounds useful in the present invention are described in WO 98/40375, and WO 00/38725, herein incorporated by reference. Additional IBAT inhibitor compounds useful in the present invention are described in U.S. application Ser. No. 08/816,065, herein incorporated by reference. In another aspect, the second biologically active agent is a statin. Statins lower cholesterol by inhibiting of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, a key enzyme in the cholesterol biosynthetic pathway. The statins decrease liver cholesterol biosynthesis, which increases the production of LDL receptors thereby decreasing plasma total and LDL cholesterol (Grundy, S. M. New Engl. J. Med. 319, 24 (1988); Endo, A. J. Lipid Res. 33, 1569 (1992)). Depending on the agent and the dose used, statins may decrease plasma triglyceride levels and may increase HDLc. Currently the statins on the market are lovastatin (Merck), simvastatin (Merck), pravastatin (Sankyo and Squibb) and fluvastatin (Sandoz). A fifth statin, atorvastatin (Parke-Davis/Pfizer), is the most recent entrant into the statin market. Any of these statins or thers can be used in combination with the chalcones of the present invention. MTP inhibitor compounds useful in the combinations and methods of the present invention comprise a wide variety of structures and functionalities. Some of the MTP inhibitor compounds of particular interest for use in the present invention are disclosed in WO 00/38725, the disclosure from which is incorporated by reference. Descriptions of these therapeutic compounds can be found in Science, 282, Oct. 23, 1998, pp. 751–754, herein incorporated by reference. Cholesterol absorption antagonist compounds useful in the combinations and methods of the present invention comprise a wide variety of structures and functionalities. Some of the cholesterol absorption antagonist compounds of particular interest for use in the present invention are described in U.S. Pat. No. 5,767,115, herein incorporated by reference. Further cholesterol absorption antagonist compounds of particular interest for use in the present invention, and methods for making such cholesterol absorption antagonist compounds are described in U.S. Pat. No. 5,631,365, herein incorporated by reference. A number of phytoisterols suitable for the combination therapies of the present invention are described by Ling and Jones in “Dietary Phytosterols: A Review of Metabolism, Benefits and Side Effects,” Life Sciences, 57 (3), 195–206 (1995). Without limitation, some phytosterols of particular use in the combination of the present invention are Clofibrate, Fenofibrate, Ciprofibrate, Bezafibrate, Gemfibrozil. The structures of the foregoing compounds can be found in WO 00/38725. Phytosterols are also referred to generally by Nes ( Physiology and Biochemistry of Sterols , American Oil Chemists' Society, Champaign, Ill., 1991, Table 7-2). Especially preferred among the phytosterols for use in the combinations of the present invention are saturated phytosterols or stanols. Additional stanols are also described by Nes (Id.) and are useful in the combination of the present invention. In the combination of the present invention, the phytosterol preferably comprises a stanol. In one preferred embodiment the stanol is campestanol. In another preferred embodiment the stanol is cholestanol. In another preferred embodiment the stanol is clionastanol. In another preferred embodiment the stanol is coprostanol. In another preferred embodiment the stanol is 22,23-dihydrobrassicastanol. In another embodiment the stanol is epicholestanol. In another preferred embodiment the stanol is fucostanol. In another preferred embodiment the stanol is stigmastanol. Another embodiment the present invention encompasses a therapeutic combination of a compound of the present invention and an HDLc elevating agent. In one aspect, the second HDLc elevating agent can be a CETP inhibitor. Individual CETP inhibitor compounds useful in the present invention are separately described in WO 00/38725, the disclosure of which is herein incorporated by reference. Other individual CETP inhibitor compounds useful in the present invention are separately described in WO 99/14174, EP818448, WO 99/15504, WO 99/14215, WO 98/04528, and WO 00/17166, the disclosures of which are herein incorporated by reference. Other individual CETP inhibitor compounds useful in the present invention are separately described in WO 00/18724, WO 00/18723, and WO 00/18721, the disclosures of which are herein incorporated by reference. Other individual CETP inhibitor compounds useful in the present invention are separately described in WO 98/35937 as well as U.S. Pat. Nos. 6,313,142, 6,310,075, 6,197,786, 6,147,090, 6,147,089, 6,140,343, and 6,140,343, the disclosures of which is herein incorporated by reference. In another aspect, the second biologically active agent can be a fibric acid derivative. Fibric acid derivatives useful in the combinations and methods of the present invention comprise a wide variety of structures and functionalities which have been reported and published in the art. In another embodiment the present invention encompasses a therapeutic combination of a compound of the present invention and an antihypertensive agent. Hypertension is defined as persistently high blood pressure. In another embodiment, the chalcone is administered in combination with an ACE inhibitor, a beta andrenergic blocker, alpha andrenergic blocker, angiotensin II receptor antagonist, vasodilator and diuretic. Pharmaceutical Compositions Any host organism, including a pateint, mammal, and specifically a human, suffering from any of the above-described conditions can be treated by the administration of a composition comprising an effective amount of the compound of the invention or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier or diluent. The composition can be administered in any desired manner, including oral, topical, parenteral, intravenous, intradermal, intra-articular, intra-synovial, intrathecal, intra-arterial, intracardiac, intramuscular, subcutaneous, intraorbital, intracapsular, intraspinal, intrastemal, topical, transdermal patch, via rectal, vaginal or urethral suppository, peritoneal, percutaneous, nasal spray, surgical implant, internal surgical paint, infusion pump, or via catheter. In one embodiment, the agent and carrier are administered in a slow release formulation such as an implant, bolus, microparticle, microsphere, nanoparticle or nanosphere. For standard information on pharmaceutical formulations, see Ansel, et al., Pharmaceutical Dosage Forms and Drug Delivery Systems , Sixth Edition, Williams & Wilkins (1995). An effective dose for any of the herein described conditions can be readily determined by the use of conventional techniques and by observing results obtained under analogous circumstances. In determining the effective dose, a number of factors are considered, including, but not limited to: the species of patient; its size, age, and general health; the specific disease involved; the degree of involvement or the severity of the disease; the response of the individual patient; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; and the use of concomitant medication. Typical systemic dosages for all of the herein described conditions are those ranging from 0.1 mg/kg to 500 mg/kg of body weight per day as a single daily dose or divided daily doses. Preferred dosages for the described conditions range from 5–1500 mg per day. A more particularly preferred dosage for the desired conditions ranges from 25–750 mg per day. Typical dosages for topical application are those ranging from 0.001 to 100% by weight of the active compound. The compound is administered for a sufficient time period to alleviate the undesired symptoms and the clinical signs associated with the condition being treated. The active compound is included in the pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver to a patient a therapeutic amount of compound in vivo in the absence of serious toxic effects. The concentration of active compound in the drug composition will depend on absorption, inactivation, and excretion rates of the drug as well as other factors known to those of skill in the art. It is to be noted that dosage values will also vary with the severity of the condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that the dosage ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed composition. The active ingredient may be administered at once, or may be divided into a number of smaller doses to be administered at varying intervals of time. A preferred mode of administration of the active compound for systemic delivery is oral. Oral compositions will generally include an inert diluent or an edible carrier. They may be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches or capsules. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring. When the dosage unit form is a capsule, it can contain, in addition to material of the above type, a liquid carrier such as a fatty oil. In addition, dosage unit forms can contain various other materials which modify the physical form of the dosage unit, for example, coatings of sugar, shellac, or other enteric agents. The compound or its salts can be administered as a component of an elixir, suspension, syrup, wafer, chewing gum or the like. A syrup may contain, in addition to the active compounds, sucrose as a sweetening agent and certain preservatives, dyes and colorings and flavors. The compound can also be mixed with other active materials that do not impair the desired action, or with materials that supplement the desired action. The compounds can also be administered in combination with nonsteroidal antiinflammatories such as ibuprofen, indomethacin, fenoprofen, mefenamic acid, flufenamic acid, sulindac. The compound can also be administered with corticosteriods. Solutions or suspensions used for parenteral, intradermal, subcutaneous, or topical application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. If administered intravenously, preferred carriers are physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In a preferred embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) are also preferred as pharmaceutically acceptable carriers. These may be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811 (which is incorporated herein by reference in its entirety). For example, liposome formulations may be prepared by dissolving appropriate lipid(s) (such as stearoyl phosphatidyl ethanolamine, stearoyl phosphatidyl choline, arachadoyl phosphatidyl choline, and cholesterol) in an inorganic solvent that is then evaporated, leaving behind a thin film of dried lipid on the surface of the container. An aqueous solution of the compound is then introduced into the container. The container is then swirled by hand to free lipid material from the sides of the container and to disperse lipid aggregates, thereby forming the liposomal suspension. Suitable vehicles or carriers for topical application can be prepared by conventional techniques, such as lotions, suspensions, ointments, creams, gels, tinctures, sprays, powders, pastes, slow-release transdermal patches, suppositories for application to rectal, vaginal, nasal or oral mucosa. In addition to the other materials listed above for systemic administration, thickening agents, emollients and stabilizers can be used to prepare topical compositions. Examples of thickening agents include petrolatum, beeswax, xanthan gum, or polyethylene, humectants such as sorbitol, emollients such as mineral oil, lanolin and its derivatives, or squalene. Any of the compounds described herein for combination or alternation therapy can be administered as any derivative that upon administration to the recipient, is capable of providing directly or indirectly, the parent compound, or that exhibits activity itself. Nonlimiting examples are the pharmaceutically acceptable salts (alternatively referred to as “physiologically acceptable salts”), and a compound which has been alkylated or acylated at an appropriate position. The modifications can affect the biological activity of the compound, in some cases increasing the activity over the parent compound. This can easily be assessed by preparing the derivative and testing its anti-inflammatory activity according to known methods. Biological Activity of Active Compounds The ability of a compound described herein to inhibit the expression of VCAM-1 or in the treatment of diseases in a host can be assessed using any known method, including that described in detail below. In Vitro MCP-1 Activity Assay Cultured human endothelial cells were seeded in 96-well plates. On the following day cells were stimulated with TNF-α (1 ng/ml) in the presence or absence of compounds dissolved in DMSO. To establish a dose curve and an IC 50 , multiple concentrations in 2- to 5-fold increments were used. Cells were exposed to TNF-α and compounds for approximately 16 hours. The next day the cells were visually examined via light microscopy to score for visual signs of toxicity. Cell culture media, diluted 1:10, was analyzed by an MCP-1 immunoassay kit (R & D Systems). This assay is a sandwich immunoassay using immobilized anti-MCP-1 antibody in 96-well plate to capture secreted MCP-1 in cell culture media. Captured MCP-1 was subsequently detected with a horse radish peroxidase-conjugated anti-MCP-1 antibody for color development. Compound 3 expressed an IC 50 values of >10(the amount of compound (μM) required to achieve a 50% reduction compared to control (cells stimulated with TNF-α only)). In Vitro VCAM-1 Assay Cell Culture and compound dosing: Cultured primary human aortic (HAEC) or pulmonary (HPAEC) endothelial cells were obtained from Clonetics, Inc., and were used below passage 9. Cells were seeded in 96 well plates such that they would reach 90–95% confluency by the following day. On the following day the cells were stimulated with TNF-α (1 ng/ml) in the presence or absence of compounds dissolved in DMSO such that the final concentration of DMSO is 0.25% or less. To establish a dose curve for each compound, four concentrations in 2- to 5-fold increments were used. Cells were exposed to TNF-α and compounds for approximately 16 hours. The next day the cells were examined under microscope to score for visual signs of toxicity or cell stress. Following 16 hr exposure to TNF-α and compound the media was discarded and the cells were washed once with Hanks Balanced Salt Solution (HBSS)/Phosphate buffered saline (PBS) (1:1). Primary antibodies against VCAM-1 (0.25 μg/ml in HBSS/PBS+5% FBS) were added and incubated for 30–60 minutes at 37° C. Cells were washed with HBSS/PBS three times, and secondary antibody Horse Radish Peroxidase (HRP)-conjugated goat anti-mouse IgG (1:500 in HBSS/PBS+5% FBS) were added and incubated for 30 minutes at 37° C. Cells were washed with HBSS/PBS four time and TMB substrate were added and incubated at room temperature in the dark until there was adequate development of blue color. The length of time of incubation was typically 5–15 minutes. 2N sulfuric acid was added to stop the color development and the data was collected by reading the absorbance on a BioRad ELISA plate reader at OD 450 nm. The results are expressed as IC 50 values (the concentration (micromolar) of compound required to inhibit 50% of the maximal response of the control sample stimulated by TNF-α only). Compounds exhibiting IC 50 's of less than 5 micromolar are tabulated in Biological Table 1. TABLE 1BiologicalVCAM-1ExampleIC50Number(μM)1<12<53<14<105<16<17<18<19<510<511<512<513<514<115>1016<517<518<519<120>1021<522>1023<124>1025>1026>1027<528<529<130<131>1032<533<534>1035>1036<537>1038<1039>1040<141<542<543<544<145<546<1047>1048<1049<1050>1051<552>1053<554<1055<556<157<558>1059NE60<161<162<563<1064>1065<166<167<1068<569<570<571NE72073074>1075>1076>1077<578<1079<180<581<182NE83<184<585<186<587<18889NE90<191<592<193<194<195<196<597NE98<599>10100>10101>10102>10103>10104NE105NE106<10107NE108<10109NE110>10111>10112NE113<5114<5115<5116117<5118<10119120<1 Rheumatoid Arthritis Protocol Male Lewis rats (150–175 g) from Charles River Laboratories were anesthetized on day 0 with 3–5% isoflurane anesthesia while the tail base was shaved and adjuvant mixture was injected. Fifty μL of adjuvant (10 mg/ml M. butyricum in mineral oil) was injected subcutaneously into two sites at the tail base. Paw swelling was monitored using a plethysmometer (UGO Basile), after shaving each leg to the level of the Achilles tendon to mark the level of immersion. A baseline paw measurement for both hindpaws was taken between d2-d5 and a second measurement was taken on day 7–8. Onset of paw swelling occurred rapidly between d9–11 and daily measurements were performed every weekday between d9 and day 15. Compounds of the invention and vehicles were dosed either prophylactically (d1–14), or therapeutically (d9–14) after swelling was confirmed. Solutions were injected subcutaneously or given orally by gavage 1–2 times per day. From day 0, rats were weighed every 2–3 days and overall health was monitored. Plasma drug levels, if desired, were measured in tail-vein derived blood samples taken on day 14. On day 15, blood samples were obtained by cardiac puncture, rats were euthanized with CO 2 , selected organs removed and both hindpaws were amputated and placed in 10% buffered formalin for histopathological analysis. See Biological Table 2. BIOLOGICAL TABLE 2Compound Example% Inhibition 60 mg/Kg/day,Numbersq, bid, d1–1439667729826062**75 mg/kg/day, sq, bid, dl–14 Asthma Protocol Balb/C mice (6–8 weeks old) are sensitized to ovalbumin (ova) (8 ug ova absorbed in 3.3 mg Alum inject) on days 0 and 5. On day 12, the mice were aerosol challenged with 0.5% ovalbumin dissolved in sterile saline for 1 hr in the AM, and then again in the PM (at least 4 hr apart). On day 14, the mice were anesthetized with ketamine/xylazine/acepromazine cocktail, exsanguinated, and then euthanized. Following blood collection, bronchoaveolar lavage was performed on each animal. Total cell counts were conducted on the lavage fluid, which was subsequently diluted with cell media 1:1. Slides of the lavage fluid were made by spinning the samples with a cytospin centrifuge. Slides were airdried and stained with x. Cell differentials of the lavage fluid were completed at the conclusion of the study. All compounds except Example 2 were well tolerated with no body weight loss throughout the course of the study. Statistical analysis involved ANOVA and Tukey-Kramer post hoc tests. Compounds were administered except where noted by subcutaneous injection once daily from day 0–13. The formulations used contained various mixtures of the following excipients (pharmasolve, cremophor RH 40, tween 80, PEG 300). See Biological Table 3 BIOLOGICAL TABLE 3% Inhibition sc, dailydosing at 100 mg/kgCompound Example Numberfrom day 0–133796818648367160362924 Effect of Serum IgE Levels in Ovalbumin Sensitized Balb/c Mice Peripheral blood samples were collected from ovalbumin (Calbiochem) or vehicle (2% Cremophor/Bicarbonate) treated Balb/c mice (Charles River) with or without administration of test compound (100 mg/kg/d, from day 0 to day 14). Serum was obtained by centrifugation and transferred into Microtainer serum tubes and frozen at −80° C. Mouse IgE ELISA Quantitation Kit (Bethyl Laboratories, Inc. Montgomery, Tex. or PharMingen, San Diego, Calif.) was applied to measure the IgE levels of serum samples. Immuno-reactions were performed as Kit protocol with IgE standard and serum samples in duplicates. The results were read in a microplate reader (Bio-Rad Model 550) at 450 nm and the amounts of IgE were calculated according to the standard curve. The limit of detection in our experiments was 7 ng/ml. Compound 3 administrated at 100 mg/kg/d from day 0 to day 14, reduced serum IgE levels by 38% in ovalbumin sensitized Balb/c mice compared with vehicle treated mice. Effect of Levels of IL-13, IL-5, IL4, IFN-Gamma and IL-2 mRNA in Mouse Lungs of Balb/c Mice with Ovalbumin Sensitization and Challenge Lung tissues were collected from ovalbumin (Calbiochem) or vehicle (2% Cremophor/Bicarbonate) sensitized Balb/c mice (Charles River) with or without treatment of test compound (100 mg/kg/d, from day 0 to day 14). Total RNA samples were isolated by the Trizol method (Life Technologies, Grand Island, N.Y.) and quantitatively measured by UV spectrophotometer, as well as qualitatively examined by ethidum bromide stained gel electrophoresis. First strand cDNA templates were generated with oligo (dT) by Reverse Transcription Kit (Invitrogen, Carlsbad, Calif.). The initial amounts of mRNA of each samples were quantitatively determined by running a SYBR Green (Qiagen, Valencia, Calif.) based real-time PCR (programmed as: initial denaturation at 95° C. for 15 minutes, denaturation at 95° C. for 15 seconds, annealing and elongation at 51±1° C. for 1 minute for total 40 cycles) with a specific pair of primers (IDT Corporation, Coralville, Iowa) and control primers for GAPDH in iCycler IQ Optical System (Hercules, Calif.). The data were statistically analyzed by ANOVA and t-tests with multiple comparisons of means (n=5 and P<0.05 were considered significant). Compound 3 administrated at 100 mg/kg/d, significantly inhibited ovalbumin induced levels of IL-13, IL-5 and IL-4 mRNA in the lung of Balb/c mice by 82%, 98% and 68% respectively; without significantly affecting IFN-gamma and IL-2 compared with vehicle treated mice. List of Primers used in above experiments:PrimerAnnealingNameForward SequenceReverse SequenceTemperatureGAPDHCTA CCC CCA ATG TGT CCCTG CTT CAC CAC CTT CTT52.2IL-13AAF AFF AGA GCA AAT GAA AGCTG TGT AAC CTT CCC AAC A51.3IL-4TGA ATG AGT CCA AGT CCAAGC ATG GTG GCT CAG TA51.2IL5AGC TCT GTT GAC AAG CAA TCCC TGA AAG ATT TCT CCA ATG52.4IL-2GTC GAC TTT CTG AGG AGA TGATG TGT TGT AAG GAG GAG GT53.2IFN-γTTC TGT CTC CTC AAC TAT TTC TCAA TCA CAG TCT TGG CTA AT51.3 Smooth Muscle Cell Proliferation Protocol Human Aortic Smooth Mucle Cells (HAoSMC) were obtained from Clonetics, Inc. and were used below passage 10. Cells were seeded in 24-well plates. When cells were 80% confluent, they were made quiescent by adding media containing 0.2% serum (as compared to 5% serum in normal culture media) for 48 hours. The cells were, then, stimulated by 5% serum in the presence or absence of compounds dissolved in DMSO. To establish a dose curve and IC 50 for each compound, multiple concentrations in the range of 20 to 0.05 μM were used. Rapamycin (at 1 and 0.1 μM) was used as a positive control for the assay. After a 20 hour incubation with or without test compounds, 3H-thymidine (0.5 μCi/well) was added to the cells for 4 hours of labeling. Washed cells were then lysed in NaOH and the amount of 3H-thymidine incorporation was determined. Cytotoxicity of the drug was measured by use of the CytolTox 96 assay kit (Promega, Madison, Wis.). Compound 3 had an IC 50 of 0.5 μM. Effect of Test Compounds on LPS-Stimulated IL-1β Human peripheral blood mononuclear cells were treated with or without Compound 3 for 1 hour, then stimulated with LPS (1–2 μg/ml) for 3 hours. Condition media was collected and IL-1β measured using an ELISA kit. Compound 3 demonstrated a dose dependent inhibition of LPS-stimulated IL-1β secretion. See Biological Table 4 BIOLOGICAL TABLE 4Amount of Compound 3(μM)Percent IL-1β Secreted1.25>402.5>105>510>1 Reduction of Plasma TNF-α Levels and Lung VCAM-1 mRNA Levels in LPS-Challenged Mice. Balb/C mice (6–8 weeks) were injected with LPS (1 mg/kg; 5 mls/kg) and sacrificed 2 hr later. Blood was collected for plasma TNF-α levels and lungs for measurement of VCAM-1 mRNA levels by quantitative RT-PCR. Compound 3 administered subcutaneously at a dose of 100 mg/kg/d, 2 hr prior to LPS injection, inhibited TNF-α production by 80% and VCAM-1 expression by 60% compared with vehicle controls. Disease Modifying Anti-Rheumatic Drug (DMARD) Activity in Rat Adjuvant Arthritis Compound 3 at twice daily subcutaneous doses of 60, 40 and 20 mg/kg/d was found to inhibit bone erosion in the ankle joint by histopathological analysis when administered prophylactically in the rat adjuvant arthritis model. The evaluation was carried out with hematoxylin and eosin stained ankle cross sections by a certified veterinary pathologist. When dosed prophylactically at doses of 100, 50 and 25 mg/kg/d, b.i.d., s.c., Compound 3 was also found to inhibit splenomegaly. Splenomegaly tracks with bone erosion in the adjuvant arthritis model and is thought to be a predictor of DMARDs activity. Modifications and variations of the present invention relating to compounds and methods of treating diseases will be obvious to those skilled in the art from the foregoing detailed description of the invention. Such modifications and variations are intended to come within the scope of the appended claims.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"}},"description_lang":["en"],"has_description":true,"has_docdb":true,"has_inpadoc":true,"has_full_text":true,"biblio_lang":"en"},"jurisdiction":"US","collections":[],"usersTags":[],"lensId":"111-352-037-735-89X","publicationKey":"US_7094801_B2","displayKey":"US 7094801 B2","docAssets":{"lensId":"111-352-037-735-89X","pdfUrl":"https://www.lens.org/images/patent/US/7094801/B2/US_7094801_B2.pdf","images":[{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000001.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000001.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000002.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000002.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000003.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000003.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000004.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000004.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000005.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000005.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000006.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000006.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000007.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000007.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000008.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000008.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000009.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000009.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000010.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000010.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000011.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000011.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000012.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000012.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000013.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000013.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000014.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000014.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000015.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000015.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000016.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000016.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000017.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000017.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000018.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000018.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000019.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000019.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000020.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000020.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000021.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000021.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000022.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000022.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000023.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000023.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000024.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000024.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000025.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000025.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000026.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000026.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000027.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000027.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000028.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000028.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000029.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000029.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000030.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000030.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000031.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000031.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000032.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000032.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000033.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000033.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000034.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000034.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000035.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000035.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000036.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000036.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000037.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000037.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000038.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000038.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000039.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000039.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000040.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000040.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000041.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000041.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000042.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000042.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000043.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000043.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000044.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000044.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000045.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000045.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000046.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000046.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000047.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000047.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000048.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000048.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000049.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000049.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000050.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000050.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000051.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000051.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000052.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000052.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000053.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000053.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000054.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000054.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000055.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000055.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000056.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000056.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000057.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000057.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000058.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000058.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000059.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000059.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000060.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000060.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000061.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000061.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000062.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000062.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000063.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000063.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000064.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000064.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000065.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000065.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000066.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000066.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000067.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000067.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000068.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000068.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000069.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000069.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000070.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000070.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000071.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000071.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000072.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000072.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000073.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000073.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000074.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000074.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000075.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000075.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000076.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000076.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000077.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000077.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000078.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000078.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000079.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000079.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000080.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000080.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000081.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000081.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000082.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000082.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000083.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000083.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000084.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000084.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000085.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000085.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000086.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000086.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000087.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000087.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000088.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000088.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000089.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000089.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000090.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000090.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000091.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000091.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000092.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000092.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000093.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000093.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000094.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000094.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000095.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000095.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000096.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000096.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000097.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000097.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000098.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000098.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000099.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000099.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000100.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000100.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000101.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000101.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000102.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000102.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000103.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000103.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000104.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000104.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000105.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000105.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000106.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000106.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000107.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000107.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000108.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000108.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000109.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000109.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000110.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000110.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000111.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000111.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000112.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000112.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000113.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000113.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000114.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000114.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000115.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000115.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000116.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000116.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000117.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000117.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000118.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000118.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000119.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000119.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000120.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000120.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000121.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000121.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000122.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000122.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000123.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000123.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000124.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000124.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000125.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000125.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000126.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000126.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000127.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000127.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000128.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000128.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000129.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000129.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000130.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000130.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000131.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000131.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000132.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000132.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000133.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000133.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000134.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000134.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000135.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000135.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000136.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000136.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000137.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000137.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000138.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000138.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000139.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000139.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000140.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000140.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000141.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000141.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000142.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000142.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000143.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000143.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000144.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000144.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000145.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000145.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000146.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000146.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000147.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000147.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000148.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000148.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000149.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000149.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000150.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000150.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000151.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000151.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000152.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000152.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000153.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000153.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000154.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000154.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000155.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000155.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000156.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000156.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000157.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000157.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000158.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000158.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000159.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000159.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000160.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000160.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000161.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000161.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000162.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000162.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000163.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000163.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000164.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000164.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000165.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000165.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000166.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000166.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000167.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000167.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000168.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000168.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000169.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000169.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000170.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000170.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000171.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000171.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000172.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000172.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000173.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000173.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000174.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000174.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000175.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000175.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000176.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000176.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000177.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000177.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000178.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000178.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000179.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000179.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000180.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000180.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000181.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000181.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000182.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000182.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000183.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000183.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000184.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000184.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000185.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000185.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000186.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000186.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000187.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000187.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000188.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000188.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000189.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000189.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000190.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000190.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000191.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000191.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000192.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000192.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000193.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000193.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000194.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000194.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000195.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000195.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000196.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000196.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000197.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000197.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000198.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000198.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000199.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000199.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000200.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000200.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000201.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000201.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000202.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000202.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000203.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000203.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000204.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000204.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000205.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000205.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000206.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000206.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000207.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000207.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000208.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000208.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000209.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000209.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000210.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000210.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000211.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000211.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000212.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000212.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000213.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000213.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000214.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000214.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000215.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000215.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000216.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000216.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000217.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000217.png"},{"thumb":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/10pc/00000218.png","full":"https://s3-us-west-2.amazonaws.com/lens-resource/patent/US/B2/7094/7094801/image/page/full/00000218.png"}],"fallover":false},"countryName":"USA","inventorModel":{"inventors":[{"name":{"value":"SIKORSKI JAMES A","valueNormalised":"Sikorski James A"},"inventorship":null},{"name":{"value":"MENG CHARLES Q","valueNormalised":"Meng Charles Q"},"inventorship":null},{"name":{"value":"WEINGARTEN M DAVID","valueNormalised":"Weingarten M David"},"inventorship":null},{"name":{"value":"WORSENCROFT KIMBERLY J","valueNormalised":"Worsencroft Kimberly J"},"inventorship":null},{"name":{"value":"NI LIMING","valueNormalised":"Ni Liming"},"inventorship":null}],"inventorships":[],"unmatchedInventorships":[],"activeUserHasInventorship":false},"simpleFamilyId":194621649,"citesPatentCount":78,"countrySpec":{"countryName":"USA","description":"GRANTED PATENT AS SECOND PUBLICATION [FROM 2001 ONWARDS]","rule":"pubdate:AFTER:01-01-2001","docType":"GRANTED_PATENT"},"pageTitle":"US 7094801 B2 - Chalcone derivatives and their use to treat diseases","documentTitle":"Chalcone derivatives and their use to treat diseases"},"claims":{"source":"xml_claims","claims":[{"lines":["A compound of Formula I\nor its pharmaceutically acceptable salt or ester, wherein:the wavy line indicates that the compound can be in the form of the E- or Z- isomer;\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein one of R2β, R3β, R4β, R5β or R6β, or one of R2α, R3α, R4α, R5α or R6α must be a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl;\n
wherein when one of R2β, R3β, R4β, R5β or R6β is a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl, only one of R2β, R3β, R4β, R5β or R6β can be —OCH3; and\n
wherein when one of R2β, R3β, R4β, R5β or R6β is a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl, only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together, or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR7R8, and halo; or\n
R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a 5- or 6-membered ring containing one sulfur, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2; provided that R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β cannot be —OC(R1)2C(O)OH; or\n
at least one of R2α, R3α, R4α, R5α, R6α or one of R2β, R3β, R4β, R5β, R6β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2, —C(CH3)2C(O)OH, (CH2)yC(O)OH, wherein is 1, 2, 3, 4, 5, or 6, thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2;\n
wherein all R1, R2, R7, and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":1,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 1 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein one of R2β, R3β, R4β, R5β or R6β, or one of R2α, R3α, R4α, R5α or R6α must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl;\n
wherein when one of R2β, R3β, R4β, R5β or R6β is a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, only one of R2β, R3β, R4β, R5β or R6β can be —OCH3; and\n
wherein when one of R2β, R3β, R4β, R5β or R6β is a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together, or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR7R8, and halo; or\n
R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a 5- or 6-membered ring containing one sulfur, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2; provided that R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β cannot be —OC(R1)2C(O)OH; and\n
at least one of R2α, R3α, R4α, or one of R2β, R3β, R4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":2,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 1 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein when one of R2β, R3β, R4β, R5β or R6β is a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together, or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR7R8, and halo; or\n
R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a 5- or 6-membered ring containing one sulfur, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2; provided that R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β cannot be —OC(R1)2C(O)OH; and\n
with the proviso that at least one of R2α, R3α, R4α, or one of R2β, R3β, R4β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":3,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 3 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R2α, R3α, R4α, R5α or R6α can be —OCH3;\n
with the proviso that R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together, or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR7R8, and halo; or\n
R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2; provided that R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β cannot be —OC(R1)2C(O)OH; and\n
with the proviso that at least one of R2α, R3α, or R4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":4,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 4 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R2α, R3α, R4α, R5α or R6α can be —OCH3;\n
with the proviso that at least one of R2α, R3α, or R4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":5,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein: R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, beteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked heterocyclic or heteroaryl, and only one of R2α, R3α, R4α, R5α or R6α can be —OCH3;\n
with the proviso that at least one of R2α, R3α, or R4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":6,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 6 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, and —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that at least one of R2α, R3α, R4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":7,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 7 or its pharmaceutically acceptable salt or ester, wherein: R5β and R6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —N(R2)C(O)R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NHC(O)NR7R8, —NHC(O)N(R2)2, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, and —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino,\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, oxo, cyano, —C(O)NR7R8, and —C(O)N(R2)2; aryl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that at least one of R2α, R3α, R4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, —C(O)NR7R8, and —C(O)N(R2)2."],"number":8,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 8 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, alkyl, lower alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, heterocyclicamino lower alkyl, hydroxyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, dialkylamino, N(R2)2, —NR7R8, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)N(R2)2, —C(O)NR7R8, —C(CH3)2C(O)OH, and —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, cycloalkyl, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 8-membered monocyclic or benzoftlsed ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that at least one of R2α, R3α, R4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, —C(O)NR7R8, and —C(O)N(R2)2."],"number":9,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 9 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, lower alkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, heteroaryl lower alkoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, carboxy, —C(O)OR2, —C(O)N(R2)2, and —C(O)NR7R8, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, hydroxy, hydroxyalkyl, heterocyclic, —NR7R8, —C(O)NR7R8, and —C(O)N(2)2;\n
R2 is independently selected from the group consisting of alkyl, and lower alkyl, wherein all may be substituted by one or more selected from the group consisting of halo, lower alkyl, —NR7R8, alkoxy, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently alkyl, and linked together forming a 5- to 7-membered monocyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that at least one of R2α, R3α, or R4α must be selected from carboxy or —C(O)OR2;\n
wherein all R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, lower alkyl, —NR7R8, —C(O)NR7R8, and —C(O)N(R2)2."],"number":10,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 10 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, heteroaryl lower alkoxy, heterocyclic lower alkoxy, and carboxy, all of which can be optionally substituted; by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR7R8, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is lower alkyl;\n
R7 and R8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that at least one of R2α, R3α, or R4α must be carboxy."],"number":11,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 11 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, and R6α are independently selected from the group consisting of hydrogen and carboxy;\n
R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR7R8, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is lower alkyl;\n
R7 and R8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl;\n
with the proviso that at least one of R2α, R3α, or R4α must be carboxy."],"number":12,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 12 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, and R6α are independently selected from the group consisting of hydrogen and carboxy;\n
R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR7R8, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is lower alkyl;\n
R7 and R8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked saturated thienyl or benzothienyl;\n
with the proviso that at least one of R2α, R3α, or R4α must be carboxy."],"number":13,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 13 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, and R6α are independently selected from the group consisting of hydrogen and carboxy;\n
R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, fluorine, chlorine, methoxy, ethoxy, propoxy, 3-(1-morpholino) propoxy, 2-(1-morpholino) ethoxy, CH3O(CH2)2O(CH2)2—,\n\n
wherein one of R4β, R5β or R6β must be selected from the group consisting of thiophen-2-yl, thiophen-3-yl, benzo[b]thiophen-2-yl, benzo[b]thiophen-3-yl,\n
with the proviso that at least one of R2α, R3α, or R4α must be carboxy."],"number":14,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 14 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, and R6α are independently selected from the group consisting of hydrogen and carboxy;\n
R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, methoxy, 3-(1-morpholino) propoxy, 2-(1-morpholino) ethoxy, and CH3O(CH2)2O(CH2)2;\n
wherein one of R4β, R5β or R6β must be selected from the group consisting of thiophen-2-yl, benzo[b]thiophen-2-yl;\n
with the proviso that at least one of R2α, R3α, or R4α must be carboxy."],"number":15,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 15 selected from the group consisting of:\n
4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid;\n
4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
2-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(3,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
2-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid, sodium salt;\n
4-[3E-(4-Thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3-{4-(thien-2-yl)-phenyl}-3-oxo-E-propenyl]-benzoic acid, sodium salt;\n
4-[3-{4-(thien-2-yl)-phenyl}-3-oxo-E-propenyl]-benzoic acid;\n
4-[3-(2-Methoxy-4-thiophen-2-yl-phenyl)-3-oxo-E-propenyl]-benzoic acid;\n
4-[3E-(4-Pyrrolidin-1-yl-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-{4-Fluoro-3-(thiophen-2-yl)-phenyl}-acryloyl]-benzoic acid;\n
4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid;\n
4-[3E-(2-Fluoro-4-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(2-Cyclopropylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(4-Methoxy-2-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
2-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
2-[3E-(2,6-Dimethoxy-4-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(2,4-Dimethoxy-6-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-{3E-[2,4-Dimethoxy-5-(5-methyl-thiophen-2-yl)-phenyl]-acryloyl}-benzoic acid;\n
4-[3E-(4-Methoxy-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(3-Thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
3-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(3-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(2-Methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-{3E-[4-(1-Carboxy-1-methyl-ethoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;\n
2-[3E-(4-Methoxy-3-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-(3E-{2-Methoxy-4-[2-(2-methoxy-ethoxy)-ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic acid;\n
4-{3E-[4-(3-Hydroxy-2-hydroxymethyl-propoxy)-2-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;\n
5-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid methyl ester;\n
5-{5-[3-(4-Carboxy-phenyl)-3-oxo-E-propenyl]-2,4-dimethoxy-phenyl}-thiophene-2-carboxylic acid;\n
4-[3E-(4-Ethoxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(4-Hydroxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid, sodium salt;\n
4-[3E-(2-Hydroxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-{3E-[2-(1-Carboxy-1-methyl-ethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;\n
4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride;\n
4-{3E-[2-(3,5-Dimethyl-isoxazol-4-ylmethoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;\n
4-[3E-(2-Pyrrolidin-1-yl-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-{3E-[2-(3-Hydroxy-2-hydroxymethyl-propoxy)-4-methoxy-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;\n
4-{3E-[2-(3-Morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride;\n
4-{3E-[4-Methoxy-2-(3-morpholin-4-yl-propoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride;\n
4-[3E-(2-Dimethylcarbamoylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(4-Methoxy-2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-[3E-(2-Carbamoylmethoxy-4-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-2-oxo-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid;\n
4-(3E-{4-Methoxy-2-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic acid, hydrochloride;\n
2-{4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-phenyl}-2-methyl-propionic acid; and\n
4-[3E-(5-Benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzoic acid ethyl ester, or its pharmaceutically acceptable salt or ester."],"number":16,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 16 selected from the group consisting of:\n
4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid;\n
4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid;\n
4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid; and\n
4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride,or its pharmaceutically acceptable salt or ester."],"number":17,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 17 wherein the compound is\n
4-[3E-(5-Benzo[b]thien-2-yl-2,4-dimethoxyphenyl)-acryloyl]-benzoic acid or its pharmaceutically acceptable salt or ester."],"number":18,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 17 wherein the compound is 4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid, or its pharmaceutically acceptable salt or ester."],"number":19,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 17 wherein the compound is 4-(3E-{4-Methoxy-2-[2-(2-methoxyethoxy)ethoxy]-5-thiophen-2-yl-phenyl}-acryloyl)-benzoic Acid; and,or its pharmaceutically acceptable salt or ester."],"number":20,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 17 wherein the compound is 4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-phenyl]-acryloyl}-benzoic acid, hydrochloride,or its pharmaceutically acceptable salt or ester."],"number":21,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, and R6α are independently selected from the group consisting of hydrogen and carboxy;\n
R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, heteroaryl, heterocyclic, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, heteroaryl lower alkoxy, and heterocyclic lower alkoxy, all of which can be optionally substituted by one or more selected from the group consisting of hydroxy, hydroxyalkyl, —NR7R8, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is lower alkyl;\n
R7 and R8 are independently alkyl, and linked together forming a 6-membered monocyclic or benzofused ring;\n
wherein one of R4β, R5β or R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl;\n
with the proviso that at least one of R2α, R3α, or R4α must be carboxy."],"number":22,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 22 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein when one of R4β, R5β, R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso at least one of R2α, R3α, R4α must be selected from the group consisting of —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":23,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein when one of R4β, R5β, R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso at least one of R2α, R3α, R4α must be selected from the group consisting of thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":24,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein when one of R4β, R5β, R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that at least one of R2α, R3α, or R4α must be selected from the group consisting of amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":25,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 5 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein when one of R4β, R5β, R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that at least one of R2α, R3α, or R4α must be selected from the group consisting of —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":26,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 3 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl loweralkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein when one of R4β, R5β, R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together, or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR7R8, and halo; and\n
with the proviso that at least one of R2α, R3α, or R4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2;\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":27,"annotation":false,"title":false,"claim":true},{"lines":["The compound of claim 3 or its pharmaceutically acceptable salt or ester, wherein:\n
R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;\n
R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;\n
wherein when one of R4β, R5β, R6β must be a carbon-carbon linked saturated or unsaturated thienyl or benzothienyl, and only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;\n
with the proviso that R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a 5- or 6-membered ring containing one nitrogen, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2; provided that R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β cannot be —OC(R1)2C(O)OH; and\n
with the proviso that at least one of R2α, R3α, or R4α must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2,\n
wherein all R1, R2, R7 and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2."],"number":28,"annotation":false,"title":false,"claim":true},{"lines":["A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28, together with one or more pharmaceutically acceptable carrier."],"number":29,"annotation":false,"title":false,"claim":true},{"lines":["A method for the treatment of an inflammatory disorder, comprising administering an effective amount of a compound of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28."],"number":30,"annotation":false,"title":false,"claim":true},{"lines":["The method of claim 30, wherein the disorder is arthritis."],"number":31,"annotation":false,"title":false,"claim":true},{"lines":["The method of claim 30, wherein the disorder is rheumatoid arthritis."],"number":32,"annotation":false,"title":false,"claim":true},{"lines":["The method of claim 30, wherein the disorder is asthma."],"number":33,"annotation":false,"title":false,"claim":true},{"lines":["The method of claim 30, wherein the treatment is disease modifying for the treatment of rheumatoid arthritis."],"number":34,"annotation":false,"title":false,"claim":true},{"lines":["The method of claim 30, wherein the disorder is allergic rhinitis."],"number":35,"annotation":false,"title":false,"claim":true},{"lines":["The method of claim 30, wherein the disorder is chronic obstructive pulmonary disease."],"number":36,"annotation":false,"title":false,"claim":true},{"lines":["The method of claim 30, wherein the disorder is atherosclerosis."],"number":37,"annotation":false,"title":false,"claim":true},{"lines":["The method of claim 30, wherein the disorder is restinosis."],"number":38,"annotation":false,"title":false,"claim":true},{"lines":["A method for inhibiting the expression of VCAM-1, comprising administering an effective amount of a compound of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28."],"number":39,"annotation":false,"title":false,"claim":true}]}},"filters":{"npl":[],"notNpl":[],"applicant":[],"notApplicant":[],"inventor":[],"notInventor":[],"owner":[],"notOwner":[],"tags":[],"dates":[],"types":[],"notTypes":[],"j":[],"notJ":[],"fj":[],"notFj":[],"classIpcr":[],"notClassIpcr":[],"classNat":[],"notClassNat":[],"classCpc":[],"notClassCpc":[],"so":[],"notSo":[],"sat":[]},"sequenceFilters":{"s":"SEQIDNO","d":"ASCENDING","p":0,"n":10,"sp":[],"si":[],"len":[],"t":[],"loc":[]}}