公开(公告)号：EP2056828A2

公开(公告)日：2009-05-13

申请号：EP07837000.4

申请日：2007-08-17

申请人： Merck & Co., Inc.

发明人： FLETCHER, Joan, M. ,  FONG, Tung, M. ,  HAGMANN, William, K. ,  VACHAL, Petr

IPC分类号： A61K31/4965 ,  A61K31/497

CPC分类号： A61K31/496

摘要： Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer’s disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson’s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.

公开(公告)号：EP2019593A1

公开(公告)日：2009-02-04

申请号：EP07794759.6

申请日：2007-05-11

申请人： Merck & Co., Inc.

发明人： HAGMANN, William, K. ,  HAMMOND, Milton, L.

IPC分类号： A01N57/00 ,  A61K31/66

CPC分类号： C07D213/64

摘要： The compounds of the present invention are prodrugs of modulators of the Cannabinoid-1 (CB 1 ) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the Cannabinoid- 1 (CB 1) receptor. In particular, compounds of the present invention are 5 prodrugs of antagonists or inverse agonists of the CB1 receptor. The invention is concerned with the use of these compounds to be converted to compounds that modulate the Cannabinoid-1 (CB 1 ) receptor. As such, the compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer's disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain- 10 Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia.

公开(公告)号：EP1017382B1

公开(公告)日：2006-03-01

申请号：EP98924988.3

申请日：1998-05-29

申请人： Merck & Co., Inc. (a New Jersey corp.)

发明人： DURETTE, Philippe, L. ,  HAGMANN, William, K. ,  MacCOSS, Malcolm ,  MILLS, Sander, G. ,  MUMFORD, Richard, A.

IPC分类号： C07K14/705 ,  A61K31/42 ,  A61K31/415 ,  A61K31/425 ,  A61K31/505 ,  C07C255/03 ,  C07D207/08 ,  C07D217/18 ,  C07D231/04 ,  C07D263/04 ,  C07D277/04 ,  C07K5/06

CPC分类号： C07K5/06165 ,  A61K38/00 ,  C07K5/06139 ,  C07K5/06191

摘要： Compounds of formula (I) are antagonists of VLA-4 and/or alpha 4 beta 7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of asthma, allergies, inflammation, multiple sclerosis, and other inflammatory and autoimmune disorders.

公开(公告)号：EP1496838A2

公开(公告)日：2005-01-19

申请号：EP03714051.4

申请日：2003-03-07

申请人： Merck & Co., Inc.

发明人： HAGMANN, William, K. ,  LIN, Linus, S. ,  SHAH, Shrenik, K. ,  GUTHIKONDA, Ravindra, N. ,  QI, Hongbo ,  CHANG, Linda, L. ,  LIU, Ping ,  ARMSTRONG, Helen, M. ,  JEWELL, James, P. ,  LANZA, Thomas, J., Jr.

IPC分类号： A61K7/00

CPC分类号： C07D213/64 ,  C07C233/13 ,  C07C235/06 ,  C07C235/20 ,  C07C235/34 ,  C07C235/74 ,  C07C235/78 ,  C07C237/06 ,  C07C255/55 ,  C07C255/60 ,  C07C271/14 ,  C07C271/22 ,  C07C275/30 ,  C07C311/03 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2602/08 ,  C07D209/34 ,  C07D209/94 ,  C07D211/34 ,  C07D213/65 ,  C07D213/68 ,  C07D215/06 ,  C07D231/12 ,  C07D233/56 ,  C07D233/70 ,  C07D237/28 ,  C07D237/32 ,  C07D239/34 ,  C07D249/04 ,  C07D249/08 ,  C07D249/12 ,  C07D263/58 ,  C07D267/14 ,  C07D277/30 ,  C07D277/36 ,  C07D295/13 ,  C07D295/15 ,  C07D513/04

摘要： Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.

摘要翻译： 结构式（I）的新型化合物是大麻素-1（CB1）受体的拮抗剂和/或反向激动剂，并且可用于治疗，预防和抑制由CB1受体介导的疾病。 本发明化合物可用作治疗精神病，记忆缺陷，认知障碍，偏头痛，神经病，包括多发性硬化症和格林 - 巴利综合征的神经炎症和病毒性脑炎的炎性后遗症，脑血管障碍 事故和头部创伤，焦虑症，压力，癫痫，帕金森病，运动障碍和精神分裂症。 该化合物还可用于治疗物质滥用障碍，肥胖或饮食失调的治疗，以及治疗哮喘，便秘，慢性肠假性梗阻和肝硬化。

公开(公告)号：EP0623143A1

公开(公告)日：1994-11-09

申请号：EP93903524.0

申请日：1993-01-15

申请人： MERCK & CO. INC.

发明人： CALDWELL, Charles, G. ,  DURETTE, Philippe, L. ,  GOULET, Joung, L. ,  HAGMANN, William, K. ,  SAHOO, Soumya, P.

IPC分类号： A61K31 ,  A61P1 ,  A61P7 ,  A61P9 ,  A61P27 ,  A61P35 ,  A61P43 ,  C07F9

CPC分类号： A61K31/675 ,  A61K31/66 ,  C07F9/301

摘要： Il a été démontré que de nouveaux composés de peptidyle contenant de l'acide phosphinique, et répondant à la formule (I), peuvent être utilisés comme inhibiteurs de maladies induites par métalloendoprotéinase matricielle, y compris l'arthrose, la polyarthrite rhumatoïde, l'arthrite septique, l'invasion tumorale dans certains cancers, les parodontolyses, l'ulcération cornéenne, la protéinurie, l'épidermolyse bulbeuse dystrophobique et les thromboses coronaires associées à la rupture des plaques athérosclérotiques. Ces inhibiteurs peuvent également être utilisés pour prévénir les séquelles pathologiques de traumatismes susceptibles de produire une invalidité permanente. Ils peuvent également être utilisés comme un moyen de régulation des naissances dans la mesure où ils peuvent prévenir l'ovulation ou l'implantation.

公开(公告)号：EP1575901A2

公开(公告)日：2005-09-21

申请号：EP03814048.9

申请日：2003-12-15

申请人： Merck & Co., Inc. (a New Jersey corp.)

发明人： LIN, Linus, S. ,  HAGMANN, William, K. ,  KUMAR, Sanjeev ,  YIN, Wenji ,  DOSS, George

IPC分类号： C07C233/05 ,  C07D213/02 ,  A61K31/44

CPC分类号： C07D213/64 ,  C07C255/60 ,  C07C275/24 ,  C07C2601/04

摘要： Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.

摘要翻译： 结构式（I）的新型化合物是大麻素-1（CB1）受体的拮抗剂和/或反向激动剂，可用于治疗，预防和抑制由CB1受体介导的疾病。 本发明的化合物可用作治疗精神病，记忆缺陷，认知障碍，偏头痛，神经病，包括多发性硬化和神经 - 巴利综合征的神经炎症性疾病以及病毒性脑炎的炎症性后遗症，脑血管 事故和头部创伤，焦虑障碍，压力，癫痫，帕金森病，运动障碍和精神分裂症。 该化合物还可用于治疗物质滥用障碍，治疗肥胖或进食障碍，以及治疗哮喘，便秘，慢性肠假性梗阻和肝硬化。

公开(公告)号：EP1499306A2

公开(公告)日：2005-01-26

申请号：EP03719642.5

申请日：2003-04-08

申请人： Merck & Co., Inc.

发明人： CASTONGUAY, Laurie, A. ,  HAGMANN, William, K. ,  LIN, Linus, S. ,  SHAH, Shrenik, K.

IPC分类号： A61K31/335 ,  A61K31/35 ,  C07D319/14 ,  C07D311/74

CPC分类号： C07D405/12 ,  C07C233/59 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/12 ,  C07D307/84 ,  C07D311/58 ,  C07D319/20

摘要： Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.

公开(公告)号：EP1490043A2

公开(公告)日：2004-12-29

申请号：EP03711667.0

申请日：2003-03-21

申请人： Merck & Co., Inc.

发明人： HAGMANN, William, K. ,  LIN, Linus, S. ,  SHAH, Shrenik, K. ,  GOULET, Mark, T. ,  JEWELL, James, P.

IPC分类号： A61K31/16 ,  A61K31/335 ,  A61K31/34 ,  A61K31/44 ,  A61K31/445 ,  C07C233/57 ,  C07D205/00 ,  C07D207/08 ,  C07D211/30 ,  C07D211/32 ,  C07D211/68 ,  C07D211/80 ,  C07D307/02 ,  C07D315/00

CPC分类号： C07D207/38 ,  C07C233/59 ,  C07C235/40 ,  C07C235/82 ,  C07C237/24 ,  C07C255/60 ,  C07C271/24 ,  C07C317/44 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07D205/04 ,  C07D207/16 ,  C07D207/48 ,  C07D211/60 ,  C07D211/62 ,  C07D213/56 ,  C07D213/61 ,  C07D213/82 ,  C07D213/89 ,  C07D265/30 ,  C07D307/24 ,  C07D307/68 ,  C07D309/08 ,  C07D401/04

摘要： Novel compounds of structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as psychotropic drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as, the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.

公开(公告)号：EP0861238A1

公开(公告)日：1998-09-02

申请号：EP96937836.0

申请日：1996-10-28

申请人： MERCK & CO., INC.

发明人： CALDWELL, Charles, G. ,  HAGMANN, William, K. ,  MacCOSS, Malcolm ,  SHAH, Shrenik, K. ,  SHANKARAN, Kothandaraman ,  FURMAN, Karla, L.

IPC分类号： A61K31 ,  A61P1 ,  A61P3 ,  A61P9 ,  A61P11 ,  A61P13 ,  A61P15 ,  A61P17 ,  A61P25 ,  A61P27 ,  A61P29 ,  A61P35 ,  A61P37 ,  A61P43 ,  C07D243 ,  C07D267 ,  C07D281 ,  C07D401 ,  C07D403 ,  C07D405 ,  C07D409 ,  C07D413 ,  C07D417 ,  C07D487 ,  C07D495 ,  C07D498 ,  C07D513

CPC分类号： C07D243/08 ,  C07D267/16 ,  C07D281/06

摘要： Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These diseases and disorders include hypotension, septic shock, toxic shock syndrome, hemodialysis, IL-2 therapy such as in cancer patients, cachexia, immunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn, eczema or psoriasis and respiratory conditions such as bronchitis, asthma, oxidant-induced lung injury and acute respiratory distress (ARDS), glomerulonephritis, restenosis, inflammatory sequelae of viral infections, myocarditis, heart failure, atherosclerosis, osteoarthritis, rheumatoid arthritis, septic arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension, retinitis and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis.

公开(公告)号：EP0586537A1

公开(公告)日：1994-03-16

申请号：EP92912475.0

申请日：1992-05-01

申请人： MERCK & CO. INC.

发明人： SAHOO, Soumya, P. ,  POLO, Scott, A. ,  DURETTE, Philippe, L. ,  ESSER, Craig, K. ,  HAGMANN, William, K. ,  KOPKA, Ihor, E. ,  CHAPMAN, Kevin, T. ,  CALDWELL, Charles, G.

IPC分类号： A61K38 ,  A61P1 ,  A61P3 ,  A61P7 ,  A61P9 ,  A61P13 ,  A61P15 ,  A61P27 ,  A61P29 ,  A61P35 ,  A61P43 ,  C07K5 ,  C07K14

CPC分类号： C07K5/022 ,  A61K38/00

摘要： On constate que les nouveaux composés N-carboxyalkylpeptidyle de la formule (I) présentent une utilité en tant qu'inhibiteurs des maladies à médiation par métalloendoprotéinase, telles que l'arthrose, la polyarthrite rheumatoïde, l'arthrite septique, l'invasion tumorale dans certains cancers, la paradontolyse, l'ulcération de la cornée, la protéineurie, l'épidermolyse bulleuse dystrophique, la thrombose coronaire associée à la rupture de plaques athéromatoses. Les métalloendoprotéinases fondamentales sont une famille de protéinases contenant du zinc renfermant de manière non exclusive de la stromélysine, de la collagénase et de la gélatinase, et qui sont capables de dégrader les principaux composants du cartilage articulaire et des membranes basales. Les inhibiteurs considérés dans la présente invention peuvent également servir à prévenir les sequelles pathologiques consécutives à des traumatismes pouvant entraîner une capacité permanente. Ces composés peuvent également servir de moyen de régulation des naissances par prévention de l'ovulation ou de l'implantation.

摘要翻译： 据发现，该新型化合物式的N- carboxyalkylpeptidyle（I）可用作métalloendoprotéinase介导的疾病，例如骨关节炎，类风湿关节炎，脓毒性关节炎，肿瘤侵袭的抑制剂 某些癌症，牙周疾病，角膜溃疡，中protéineurie，营养不良性表皮松解症，与破athéromatoses板相关联的冠状动脉血栓形成。 基本métalloendoprotéinases是包含含有不限于基质溶素，胶原酶和明胶酶锌蛋白酶的家族，并且其能够降解关节软骨和基底膜的主要成分的。 本发明中考虑的抑制剂也可以用于预防可能导致永久能力的创伤引起的病理性后遗症。 这些化合物还可以通过防止排卵或植入作为控制生育的手段。