公开(公告)号：EP1517895A1

公开(公告)日：2005-03-30

申请号：EP03760540.9

申请日：2003-06-23

申请人： MERCK FROSST CANADA INC.

发明人： DESCHENES, Denis ,  DUBE, Daniel ,  DUBE, Laurence ,  GALLANT, Michel ,  GIRARD, Yves ,  LACOMBE, Patrick ,  MACDONALD, Dwight

IPC分类号： C07D215/04 ,  C07D215/12 ,  C07D409/10 ,  C07D407/10 ,  C07D401/10 ,  C07D413/10 ,  C07D413/14 ,  C07D471/04 ,  C07D401/04 ,  C07D403/10 ,  C07D417/10 ,  A61K31/4709 ,  A61K31/47 ,  A61K31/497 ,  A61P29/00

CPC分类号： C07D215/04 ,  C07D215/06 ,  C07D215/12 ,  C07D215/14 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D403/10 ,  C07D405/10 ,  C07D407/10 ,  C07D409/10 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/12 ,  C07D471/04 ,  C07F7/0812 ,  C07F9/60

摘要： 8-(biaryl) quinolines wherein the bi-aryl group at the 8-position is in a meta relationship to the quinoline group, are PDE4 inhibitors useful in the treatment of asthma, chronic bronchitis, chronic obstructive pulmonary disease, eosinophilic granuloma, psoriasis and other benign or malignant proliferative skin diseases, endotoxic shock, laminitis in horses, colic in horses, septic shock, ulcerative colitis, Crohn's disease, reperfusion injury of the myocardium and brain, inflammatory arthritis, chronic glomerulonephritis, atopic dermatitis, urticaria, adult respiratory distress syndrome, chronic obstructive pulmonary disease in animals, diabetes insipidus, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, arterial restenosis, ortherosclerosis, atherosclerosis, neurogenic inflammation, pain, cough, rheumatoid arthritis, ankylosing spondylitis, transplant rejection, graft versus host disease, hypersecretion of gastric acid, bacterial, fungal induced sepsis, viral induced sepsis, fungal induced septic shock, viral induced septic shock, inflammation-mediated chronic tissue degeneration, cytokine-mediated chronic tissue degeneration, osteoarthritis, cancer, cachexia, muscle wasting, depression, memory impairment, tumour growth, or cancerous invasion of normal tissues.In another aspect, the present invention is directed to a method of enhancing cognition in a healthy subject comprising administering a safe cognition enhancing amount of phosphodiesterase-4 inhibitor. In particular, this invention is directed to a method of enhancing memory, learning, retention, recall, awareness and judgement in health subjects comprising administering a safe and cognition enhancing amount of a phosphodiesterase-4 inhibitor.

公开(公告)号：EP0809630A1

公开(公告)日：1997-12-03

申请号：EP96901667.0

申请日：1996-02-08

申请人： MERCK FROSST CANADA, INC.

发明人： GALLANT, Michel ,  GAREAU, Yves ,  GUAY, Daniel ,  LABELLE, Marc ,  PRASIT, Petpiboon

IPC分类号： C07D401 ,  A61K31 ,  A61P11 ,  A61P25 ,  A61P27 ,  A61P29 ,  A61P37 ,  A61P43 ,  C07D209 ,  C07D403 ,  C07D405 ,  C07D409

CPC分类号： C07D209/14 ,  C07D209/26

摘要： Disclosed are indole derivatives of formula (I) having activity on the cannabinoid receptors and the methods of their preparation. The compounds are useful for lowering ocular intraocular pressure and treating glaucoma because of the activity of the cannabinoid receptor.

公开(公告)号：EP1244628A1

公开(公告)日：2002-10-02

申请号：EP00986937.1

申请日：2000-12-20

申请人： MERCK FROSST CANADA INC.

发明人： DESCHENES, Denis ,  DUBE, Daniel ,  GALLANT, Michel ,  GIRARD, Yves ,  LACOMBE, Patrick ,  MACDONALD, Dwight ,  MASTRACCHIO, Anthony ,  PERRIER, Helene

IPC分类号： C07D215/12 ,  A61K31/47 ,  A61K31/4709 ,  C07D215/14 ,  C07D401/10 ,  C07D413/10 ,  C07D417/10

CPC分类号： C07D401/10 ,  C07D215/12 ,  C07D215/14 ,  C07D401/14 ,  C07D405/12 ,  C07D409/10 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14

摘要： Novel substituted 8-arylquinolines represented by Formula (I), or a pharmaceutically acceptable salt thereof, wherein S1, S2 and S3 are independently H, -OH; halogen, -C1-C6alkyl, -NO2, -CN, or -C1-C6alkoxy, wherein the alkyl and alkoxy groups are optionally substituted with 1-5 substituents; wherein each substituent is independently a halogen or OH; R1 is a H, OH, halogen, carbonyl, or -C1-C6alkyl, -cycloC3-C6alkyl, -C1-C6alkenyl, -C1-C6alkoxy, aryl, heteroaryl, -CN, -heterocycloC3-C6alkyl, -amino, -C1-C6alkylamino, -(C1-C6alkyl)(C1-C6alkyl)amino, -C1-C6alkyl(oxy)C1-C6alkyl, -C(O)NH(aryl), -C(O)NH(heteroaryl), -SOnNH(aryl), -SOnNH(heteroaryl), -SOnNH(C1-C6alkyl), -C(O)N(C0-C6alkyl) (C0-C6alkyl), -NH-SOn-(C1-C6alkyl), -SOn-(C1-C6alkyl), -(C1-C6alkyl)-O-C(CN)-dialkylamino, or -(C1-C6alkyl)-SOn-(C1-C6alkal) group, wherein any of the groups is optionally substituted with 1-5 substituents; wherein each substituent is independently a halogen, -OH, -CN, -C1-C6alkyl, -cycloC3-C6alkyl, -C(O)(heterocycloC3-C6alkyl), -C(O)-O-(C0-C6alkyl), -C(O)-aryloxy, -C1-C6alkoxy, -(C0-C6alkyl)(C0-C6alkyl)amino, cycloalkyloxy, acyl, acyloxy, -cycloC3-C6alkyl, heterocycloC3-C6alkyl, aryl, heteroaryl, carbonyl, carbamoyl, or -SOn-(C1-C6alkyl); A is CH, C-ester, or C-R4; R2 and R3 independently is an aryl, heteroaryl, H, halogen, -CN, -C1-C6alkyl, heterocycloC3-6alkyl, -C1-C6alkoxy, carbonyl, carbamoyl, -C(O)OH, -C1-C6alkyl)-SOn-(C1-C6alkyl), -C(O)N(C0-C6alkyl)(C0-C6alkyl), or -C1-C6alkylacylamino group, wherein any of the groups is optionally substituted with 1-5 substituents, wherein each substituent is independently an aryl, heteroaryl, halogen, -NO2, -C(O)OH, carbonyl, -CN, -C1-C6alkyl, -SOn-(C1-C6alkyl), -SOn-(aryl), aryloxy, -heteroaryloxy, C1-C6alkoxy, N-oxide, -C(O)-heterocycloC3-C6alkyl, -NH-cycloC3-C6alkyl, amino, -OH, or -(C0-C6alkyl)(C0-C6alkyl)amino, -C(O)-N(C0-C6alkyl)(C0-C6alkyl) substituent group, wherein each substituent group independently is optionally substituted with -OH, C1-C6alkoxy, -C1-C6alkyl, -cycloC3-C6alkyl, aryloxy, -C(O)OH, -C(O)O(C1-C6alkyl), halogen, -NO2, -CN, -SOn-(C1-C6alkyl), or -C(O)-N(C0-C6alkyl)(C0-C6alkyl); one of R2 and R3 must be an aryl or heteroaryl, optionally substituted; when R2 and R3 are both an aryl or heteroaryl, then R2 and R3 may be optionally connected by a thio, oxy, or (C1-C4alkyl) bridge to form a fused three ring system; are PDE4 inhibitors.

公开(公告)号：EP0885243A1

公开(公告)日：1998-12-23

申请号：EP97907690.0

申请日：1997-02-19

申请人： MERCK & CO., INC. ,  MERCK FROSST CANADA INC.

发明人： NICHOLSON, Donald, W. ,  FAZIL, Kimberly, A. ,  GALLANT, Michel ,  GAREAU, Yves ,  LABELLE, Marc ,  RASPER, Dita, M. ,  RUEL, Rejean ,  VAILLANCOURT, John, P. ,  BECKER, Joseph, W. ,  ROTONDA, Jennifer ,  THORNBERRY, Nancy, A. ,  PETERSON, Erin, P.

IPC分类号： C12N15 ,  C07K5 ,  C07K14 ,  C12N1 ,  C12N9 ,  A61K38 ,  C12R1

CPC分类号： C12N9/6475 ,  A61K38/00 ,  C07K5/1021

摘要： The invention relates to crystallized apopain, the use of that structure to solve the structure of apopain homologues and other crystal forms of apopain, mutants and co-complexes of apopain, and the use of the apopain structure and that of its homologues, mutants, and co-complexes to design modulators of apopain.