公开(公告)号：WO2007008942A3

公开(公告)日：2007-04-12

申请号：PCT/US2006026976

申请日：2006-07-11

Applicant: AERIE PHARMACEUTICALS INC ,  DELONG MITCHELL A ,  SZNAIDMAN MARCOS L ,  OAKLEY ROBERT H ,  ECKHARDT ALLEN E ,  HUDSON CHRISTINE ,  YINGLING JEFFREY D ,  PEEL MICHAEL ,  RICHARDSON THOMAS E ,  MURRAY CLAIRE LOUISE ,  RAO BYAPPANAHALLY N NARASINGA ,  HEASLEY BRIAN H ,  PATEL PARESMA R

Inventor： DELONG MITCHELL A ,  SZNAIDMAN MARCOS L ,  OAKLEY ROBERT H ,  ECKHARDT ALLEN E ,  HUDSON CHRISTINE ,  YINGLING JEFFREY D ,  PEEL MICHAEL ,  RICHARDSON THOMAS E ,  MURRAY CLAIRE LOUISE ,  RAO BYAPPANAHALLY N NARASINGA ,  HEASLEY BRIAN H ,  PATEL PARESMA R

IPC: C07D213/61 ,  A61K31/341 ,  A61K31/381 ,  A61K31/4164 ,  A61K31/44 ,  A61K31/47 ,  A61K31/513 ,  A61P27/02 ,  C07C251/86 ,  C07D213/36 ,  C07D215/42 ,  C07D233/88 ,  C07D239/54 ,  C07D307/52 ,  C07D333/36

CPC classification number: C07D401/12 ,  C07D213/53 ,  C07D213/61 ,  C07D213/75 ,  C07D215/12 ,  C07D215/42 ,  C07D233/64 ,  C07D239/52 ,  C07D239/54 ,  C07D307/14 ,  C07D307/52 ,  C07D333/22 ,  C07D401/14

Abstract: Hydrazide compounds with GPCR desensitization inhibitory activity are provided that may be used to influence, inhibit or reduce the action of a G-protein receptor kinase. Pharmaceutical compositions including therapeutically effective amounts of the hydrazide compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions controlled or influenced by GPCRs are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer osteoporosis and glaucoma are also provided. (Formula (I)). A is selected from a heteroaryl group (i): wherein X 1 , X 2 , X 3 and X 4 are, independently, CH, O, S or N-R 6 , with the proviso that at least one of X 2 or X 3 is O, S or N-R 6 ; and a heteroaryl group (ii): wherein X 5 and X 9 are CH or C-halogen, X 6 and X 8 are CH, and X 7 is N, and wherein the six-membered heteroaryl group may be further fused with an unsubstituted six-member aryl group; R 1 , R 2 , R 3 , R 4 , and R 5 are, independently, hydrogen; halogen; C 1 -C 4 alkyl; amino; nitro; cyano; heteroaryl; carboxy, carbonylamino; aminosulfonyl; sulfonylamino; aminoacyl; thioalkyl; sulfonyl; acyl; heterocycle; -OR; -O-C 1 -C 4 alkyl-heterocycle; -C(O)NH-C 1 -C 4 alkyl-heterocycle; -C(O)NH-heteroaryl; -C(O)NH-aryl; or carboxylamino; wherein R is C 1 -C 4 alkyl; aryl, heteroaryl, C 1 -C 4 alkyl aryl or C 1 -C 4 alkyl heteroaryl; R 6 is H or C 1 -C 4 alkyl; R 7 is hydrogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy; and X is N-R 6 .

Abstract translation: 提供具有GPCR脱敏抑制活性的酰肼化合物，其可用于影响，抑制或降低G蛋白受体激酶的作用。 还提供包含治疗有效量的酰肼化合物和药学上可接受的载体的药物组合物。 还提供了使用化合物和/或组合物影响受GPCR控制或影响的疾病状态或病症的各种方法。 还提供了使用化合物和/或组合物影响疾病状态或病症如癌症骨质疏松症和青光眼的各种方法。 （式（I））。 A选自杂芳基（i）：其中X 1，X 2，X 3和X 4 >独立地是CH，O，S或NR 6，条件是X 2或X 3中的至少一个是O ，S或NR 6; 和杂芳基（ii）：其中X 5和X 9是CH或C-卤素，X 6和X 8 H是CH，X 7是N，并且其中六元杂芳基可以进一步与未取代的六元芳基稠合; R 1，R 2，R 3，R 4和R 5， 独立地是氢; 卤素; C 1 -C 4烷基; 氨基; 硝基; 氰基; 杂; 羧基，羰基氨基; 氨基磺酰基; 磺酰; 氨; 硫代; 磺酰基; 酰基; 杂环; -要么; -O-C _{1 -C 4 烷基 - 杂环; -C（O）NH-C 1 -C 4 烷基 - 杂环; -C（O）NH杂芳基; -C（O）NH-芳基; 或羧基氨基; 其中R是C 1 -C 4烷基; 芳基，杂芳基，C 1 -C 4烷基芳基或C 1 -C 4烷基杂芳基; R 6是H或C 1 -C 4烷基; R 7是氢，C 1 -C 4烷基或C 1 -C 4烷基或C 1 -C 4 - 烷氧基; X为N-R 6。}

公开(公告)号：WO2007008942A2

公开(公告)日：2007-01-18

申请号：PCT/US2006/026976

申请日：2006-07-11

Applicant: AERIE PHARMACEUTICALS, INC. ,  DELONG, Mitchell, A. ,  SZNAIDMAN, Marcos, L. ,  OAKLEY, Robert, H. ,  ECKHARDT, Allen, E. ,  HUDSON, Christine ,  YINGLING, Jeffrey, D. ,  PEEL, Michael ,  RICHARDSON, Thomas, E. ,  MURRAY, Claire, Louise ,  RAO, Byappanahally, N. Narasinga ,  HEASLEY, Brian, H. ,  PATEL, Paresma, R.

Inventor： DELONG, Mitchell, A. ,  SZNAIDMAN, Marcos, L. ,  OAKLEY, Robert, H. ,  ECKHARDT, Allen, E. ,  HUDSON, Christine ,  YINGLING, Jeffrey, D. ,  PEEL, Michael ,  RICHARDSON, Thomas, E. ,  MURRAY, Claire, Louise ,  RAO, Byappanahally, N. Narasinga ,  HEASLEY, Brian, H. ,  PATEL, Paresma, R.

CPC classification number: C07D401/12 ,  C07D213/53 ,  C07D213/61 ,  C07D213/75 ,  C07D215/12 ,  C07D215/42 ,  C07D233/64 ,  C07D239/52 ,  C07D239/54 ,  C07D307/14 ,  C07D307/52 ,  C07D333/22 ,  C07D401/14

Abstract: Hydrazide compounds with GPCR desensitization inhibitory activity are provided that may be used to influence, inhibit or reduce the action of a G-protein receptor kinase. Pharmaceutical compositions including therapeutically effective amounts of the hydrazide compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions controlled or influenced by GPCRs are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, osteoporosis and glaucoma are also provided.

Abstract translation: 提供具有GPCR脱敏抑制活性的酰肼化合物，其可用于影响，抑制或降低G蛋白受体激酶的作用。 还提供包含治疗有效量的酰肼化合物和药学上可接受的载体的药物组合物。 还提供了使用化合物和/或组合物影响受GPCR控制或影响的疾病状态或病症的各种方法。 还提供了使用化合物和/或组合物影响疾病状态或病症如癌症，骨质疏松症和青光眼的各种方法。

公开(公告)号：WO2007008926A1

公开(公告)日：2007-01-18

申请号：PCT/US2006/026947

申请日：2006-07-11

Applicant: AERIE PHARMACEUTICALS, INC. ,  DELONG, Mitchell, A. ,  SZNAIDMAN, Marcos, L. ,  OAKLEY, Robert, H. ,  ECKHARDT, Allen, E. ,  HUDSON, Christine ,  YINGLING, Jeffrey, D. ,  PEEL, Michael ,  RICHARDSON, Thomas, E. ,  MURRAY, Claire, Louise ,  RAO, Byappanahally N., Narasinga ,  HEASLEY, Brian, H. ,  PATEL, Paresma, R.

Inventor： DELONG, Mitchell, A. ,  SZNAIDMAN, Marcos, L. ,  OAKLEY, Robert, H. ,  ECKHARDT, Allen, E. ,  HUDSON, Christine ,  YINGLING, Jeffrey, D. ,  PEEL, Michael ,  RICHARDSON, Thomas, E. ,  MURRAY, Claire, Louise ,  RAO, Byappanahally N., Narasinga ,  HEASLEY, Brian, H. ,  PATEL, Paresma, R.

IPC: C07D217/02 ,  A61K31/472 ,  A61P27/06

CPC classification number: C07D217/02

Abstract: Isoquinoline compounds are provided that influence, inhibit or reduce the action of a G-protein receptor kinase . Pharmaceutical compositions including therapeutically effective amounts of the isoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, osteoporosis and glaucoma are also provided.

Abstract translation: 提供了影响，抑制或降低G蛋白受体激酶作用的异喹啉化合物。 还提供包含治疗有效量的异喹啉化合物和药学上可接受的载体的药物组合物。 还提供了使用化合物和/或组合物影响疾病状态或病症如癌症，骨质疏松症和青光眼的各种方法。