公开(公告)号：WO2014209978A1

公开(公告)日：2014-12-31

申请号：PCT/US2014/043835

申请日：2014-06-24

Applicant: MERCK PATENT GMBH ,  YU, Henry ,  RICHARDSON, Thomas E. ,  DONNELLY, Marianne ,  NGUYEN, Ngan ,  JIANG, Xuliang

Inventor： YU, Henry ,  RICHARDSON, Thomas E. ,  DONNELLY, Marianne ,  NGUYEN, Ngan ,  JIANG, Xuliang

IPC: C07D471/02 ,  C07D498/04 ,  A61K31/4188 ,  A61P5/06

CPC classification number: C07D471/04 ,  C07D471/02 ,  C07D493/14 ,  C07D498/04 ,  C07D498/14

Abstract: The present invention relates to imidazole compounds, and pharmaceutically acceptable compositions thereof, useful as positive allosteric modulators of follicle stimulating hormone receptor (FSHR).

Abstract translation: 本发明涉及可用作促卵泡激素受体（FSHR）的正变构调节剂的咪唑化合物及其药学上可接受的组合物。

公开(公告)号：WO2013012848A1

公开(公告)日：2013-01-24

申请号：PCT/US2012/047038

申请日：2012-07-17

Applicant: YU, Henry ,  LI, Jiezhen ,  RICHARDSON, Thomas E. ,  BHARATHI, Pandi ,  HEASLEY, Brian H. ,  GOUTOPOULOS, Andreas ,  MERCK PATENT GMBH

Inventor： YU, Henry ,  LI, Jiezhen ,  RICHARDSON, Thomas E. ,  BHARATHI, Pandi ,  HEASLEY, Brian H. ,  GOUTOPOULOS, Andreas

IPC: C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/10 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  A61K31/496 ,  A61P15/08

CPC classification number: C07D417/12 ,  A61K31/454 ,  A61K31/496 ,  A61K31/498 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  C07D233/64 ,  C07D263/34 ,  C07D307/68 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/10 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

Abstract: Novel benzamide derivatives of formula (I) wherein W 1 , W 2 , R 1 to R 7 , R 6 , X and Y have the meaning according to the claims, are positive allosteric modulators of the FSH receptor, and can be employed, inter alia, for the treatment of fertility disorders.

Abstract translation: 其中W 1，W 2，R 1至R 7，R 6，X和Y具有根据权利要求的含义的式（I）的新型苯甲酰胺衍生物是FSH受体的正变构调节剂，并且可以用于治疗 的生育障碍。

公开(公告)号：WO2012013282A8

公开(公告)日：2012-03-29

申请号：PCT/EP2011003272

申请日：2011-07-01

Applicant: MERCK PATENT GMBH ,  HUCK BAYARD R ,  NEAGU CONSTANTIN ,  JONES REINALDO C ,  DESELM LIZBETH CELESTE ,  XIAO YUFANG ,  KARRA SRINIVASA R ,  LAN RUOXI ,  MOCHALKIN IGOR ,  SUTTON AMANDA E ,  RICHARDSON THOMAS E

Inventor： HUCK BAYARD R ,  NEAGU CONSTANTIN ,  JONES REINALDO C ,  DESELM LIZBETH CELESTE ,  XIAO YUFANG ,  KARRA SRINIVASA R ,  LAN RUOXI ,  MOCHALKIN IGOR ,  SUTTON AMANDA E ,  RICHARDSON THOMAS E

IPC: C07D239/74 ,  A61K31/517 ,  A61P35/00 ,  C07D403/12

CPC classification number: C07D239/94 ,  A61K31/517 ,  A61K45/06 ,  C07D239/74 ,  C07D403/12

Abstract: The invention provides novel bicyclic azaheterocyciic carboxamide compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Abstract translation: 本发明提供了根据式（I）的新型双环氮杂杂环羧酰胺化合物，它们的制造和用于治疗过度增殖性疾病例如癌症的用途。

公开(公告)号：WO2010077530A1

公开(公告)日：2010-07-08

申请号：PCT/US2009/066319

申请日：2009-12-02

Applicant: MERCK PATENT GMBH ,  XIAO, Yufang ,  HUCK, Bayard, R. ,  SUTTON, Amanda, E. ,  RICHARDSON, Thomas, E. ,  KARRA, Srinivasa, R.

Inventor： XIAO, Yufang ,  HUCK, Bayard, R. ,  SUTTON, Amanda, E. ,  RICHARDSON, Thomas, E. ,  KARRA, Srinivasa, R.

IPC: C07D471/04 ,  C07D471/14 ,  C07D495/14 ,  C07D491/147 ,  A61K31/4375 ,  A61P35/00

CPC classification number: C07D471/04 ,  C07D471/14 ,  C07D491/147 ,  C07D495/14

Abstract: Disclosed are C-ring modified tricyclic benzonaphthiridinone compounds and analogs thereof, pharmaceutical compositions comprising such compounds and processes for preparing the same. The compounds are useful in the treatment of diseases amenable to protein kinase signal transduction inhibition, regulation and/or modulation.

Abstract translation: 公开了C环改性的三环苯并萘环酮化合物及其类似物，包含这些化合物的药物组合物及其制备方法。 该化合物可用于治疗适于蛋白激酶信号转导抑制，调节和/或调节的疾病。

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：WO2013006308A2

公开(公告)日：2013-01-10

申请号：PCT/US2012/044169

申请日：2012-06-26

Applicant: MERCK PATENT GMBH ,  YU, Henry ,  RICHARDSON, Thomas E. ,  FOGLESONG, Robert James ,  DESELM, Lizbeth Celeste ,  GOUTOPOULOS, Andreas

Inventor： YU, Henry ,  RICHARDSON, Thomas E. ,  FOGLESONG, Robert James ,  DESELM, Lizbeth Celeste ,  GOUTOPOULOS, Andreas

IPC: C07D231/12 ,  C07D401/04 ,  C07D401/06 ,  C07D403/06 ,  C07D405/04 ,  C07D405/06 ,  C07D405/14 ,  C07D409/04 ,  C07D409/06 ,  C07D413/06 ,  A61K31/4152 ,  A61K31/4155 ,  A61P15/08

CPC classification number: A61K31/415 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/0048 ,  A61K9/0078 ,  A61K9/06 ,  A61K9/19 ,  A61K9/2018 ,  A61K9/2059 ,  A61K9/48 ,  A61K31/4155 ,  A61K31/423 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4709 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  A61K47/06 ,  C07D231/06 ,  C07D231/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D403/04 ,  C07D403/06 ,  C07D403/10 ,  C07D405/04 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D409/04 ,  C07D409/06 ,  C07D413/06 ,  C07D413/10 ,  C07D417/10 ,  C07D471/04

Abstract: Novel dihydropyrazole derivatives of formula (I) wherein L, R, R 3 , R 4 , R 5 , R 6 , R 7 , X 1 , X 2 , X 3 , X 4 , Y, m and n have the meaning according to the claims, are positive allosteric modulators of the FSH receptor, and can be employed, inter alia, for the treatment of fertility disorders.

Abstract translation: 式（I）的新型二氢吡唑衍生物其中L，R，R3，R4，R5，R6，R7，X1，X2，X3，X4，Y，m和n具有根据权利要求的含义，是正变构调节剂 FSH受体，并且可以特别用于治疗生育障碍。

公开(公告)号：WO2012013282A1

公开(公告)日：2012-02-02

申请号：PCT/EP2011/003272

申请日：2011-07-01

Applicant: MERCK PATENT GMBH ,  HUCK, Bayard, R. ,  NEAGU, Constantin ,  JONES, Reinaldo C. ,  DESELM, Lizbeth, Celeste ,  XIAO, Yufang ,  KARRA, Srinivasa, R. ,  LAN, Ruoxi ,  MACHALKIN, Igor ,  SUTTON, Amanda, E. ,  RICHARDSON, Thomas, E.

Inventor： HUCK, Bayard, R. ,  NEAGU, Constantin ,  JONES, Reinaldo C. ,  DESELM, Lizbeth, Celeste ,  XIAO, Yufang ,  KARRA, Srinivasa, R. ,  LAN, Ruoxi ,  MACHALKIN, Igor ,  SUTTON, Amanda, E. ,  RICHARDSON, Thomas, E.

IPC: C07D239/74 ,  C07D403/12 ,  A61K31/517 ,  A61P35/00

CPC classification number: C07D239/94 ,  A61K31/517 ,  A61K45/06 ,  C07D239/74 ,  C07D403/12

Abstract: The invention provides novel bicyclic azaheterocyciic carboxamide compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Abstract translation: 本发明提供了根据式（I）的新型双环氮杂胞苷酰胺化合物，其用于治疗过度增殖性疾病如癌症的制备和用途。

公开(公告)号：WO2011017009A1

公开(公告)日：2011-02-10

申请号：PCT/US2010/042844

申请日：2010-07-22

Applicant: MERCK PATENT GMBH ,  SUTTON, Amanda E. ,  BRUGGER, Nadia ,  RICHARDSON, Thomas E. ,  VANDEVEER, Harold George ,  HUCK, Bayard R. ,  LAN, Ruoxi ,  POTNICK, Justin

Inventor： SUTTON, Amanda E. ,  BRUGGER, Nadia ,  RICHARDSON, Thomas E. ,  VANDEVEER, Harold George ,  HUCK, Bayard R. ,  LAN, Ruoxi ,  POTNICK, Justin

IPC: C07D471/04 ,  C07D487/04 ,  A61K31/437 ,  A61K31/519 ,  A61P35/00

CPC classification number: C07D471/04 ,  C07D333/02 ,  C07D487/04

Abstract: The invention provides novel substituted azaheterocyclic compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Abstract translation: 本发明提供根据式（I）的新型取代的氮杂环化合物，其用于治疗过度增殖性疾病如癌症的制备和用途。

公开(公告)号：WO2010093419A1

公开(公告)日：2010-08-19

申请号：PCT/US2010/000313

申请日：2010-02-04

Applicant: MERCK PATENT GMBH ,  SUTTON, Amanda E. ,  RICHARDSON, Thomas E. ,  HUCK, Bayard R. ,  KARRA, Srinivasa R. ,  CHEN, Xiaoling ,  XIAO, Yufang ,  GOUTOPOULOS, Andreas ,  LAN, Ruoxi ,  PERREY, David ,  VANDEVEER, Harold, George ,  LIU-BUJALSKI, Lesley ,  STIEBER, Frank ,  HODOUS, Brian L. ,  QIU, Hui ,  JONES, Reinaldo C. ,  HEASLEY, Brian

Inventor： SUTTON, Amanda E. ,  RICHARDSON, Thomas E. ,  HUCK, Bayard R. ,  KARRA, Srinivasa R. ,  CHEN, Xiaoling ,  XIAO, Yufang ,  GOUTOPOULOS, Andreas ,  LAN, Ruoxi ,  PERREY, David ,  VANDEVEER, Harold, George ,  LIU-BUJALSKI, Lesley ,  STIEBER, Frank ,  HODOUS, Brian L. ,  QIU, Hui ,  JONES, Reinaldo C. ,  HEASLEY, Brian

IPC: C07D239/94 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D413/04 ,  A61K31/517 ,  A61P35/00

CPC classification number: C07D215/04 ,  A61K31/47 ,  C07D239/94 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D413/04

Abstract: The invention provides novel substituted amino azaheterocyclic carboxamide compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Abstract translation: 本发明提供根据式（I）的新型取代的氨基氮杂环甲酰胺化合物，其用于治疗过度增殖性疾病如癌症的制备和用途。