公开(公告)号：EP1368342B1

公开(公告)日：2005-09-07

申请号：EP01992307.7

申请日：2001-12-21

申请人： NEUROGEN CORPORATION ,  PFIZER INC.

发明人： LI, Guiying ,  PETERSON, John, M. ,  ALBAUGH, Pamela ,  CURRIE, Kevin, S. ,  CAI, Guolin ,  GUSTAVSON, Linda, M. ,  LEE, Kyungae ,  HUTCHISON, Alan ,  SINGH, Vinod ,  MAYNARD, George, D. ,  YUAN, Jun ,  LING HONG, Xie ,  GHOSH, Manuka ,  LIU, Nian ,  LUKE, George, P. ,  MITCHELL, Scott ,  ALLEN, Martin, Patrick ,  LIRAS, Spiros

IPC分类号： C07D401/14 ,  C07D403/06 ,  C07D413/14 ,  C07D403/14 ,  C07D471/04 ,  C07D417/04 ,  C07D403/04 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  A61K31/415 ,  A61P25/00

CPC分类号： C07D401/04 ,  C07D233/20 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D473/00 ,  C07D491/08 ,  C07D491/10

摘要： This invention relates to benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds, all of which may be described by of Formula (I). The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABAA receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Novel processes for preparing compounds of Formula I are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABAA receptors in tissue sections.

公开(公告)号：EP1745033A2

公开(公告)日：2007-01-24

申请号：EP05746687.2

申请日：2005-05-06

申请人： NEUROGEN CORPORATION

发明人： MAYNARD, George, D. ,  GHOSH, Manuka ,  YUAN, Jun ,  CURRIE, Kevin, S. ,  MITCHELL, Scott ,  GUO, Qin ,  ZHAO, He

IPC分类号： C07D401/04 ,  A61K31/506

CPC分类号： A61K31/505 ,  C07D239/26 ,  C07D239/28 ,  C07D239/34 ,  C07D239/42 ,  C07D239/47 ,  C07D239/48 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D417/04 ,  C07D471/04 ,  C07D498/04

摘要： 4,5-disubstituted-2-arylpyrimidines of Formula (I) and Formula (II) are provided: wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula I and II bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 4,5-disubstituted-2-arylpyrimidines, which are useful as probes for the localization of C5a receptors.

公开(公告)号：EP1745024A1

公开(公告)日：2007-01-24

申请号：EP05747952.9

申请日：2005-05-06

申请人： NEUROGEN CORPORATION

发明人： LEE, Kyungae ,  YUAN, Jun ,  MAYNARD, George, D. ,  HUTCHISON, Alan ,  MITCHELL, Scott

IPC分类号： C07D217/02 ,  A61K31/47

CPC分类号： C07D405/12 ,  A61K31/47 ,  C07D217/14 ,  C07D217/16 ,  C07D217/22 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D413/14

摘要： 1-Aryl-4-substituted isoquinolines analogues of Formula (I) and Formula (II) are provided, as follows : wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula (I) and (II) bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 1-aryl-4-substituted isoquinolines, which are useful as probes for the localization of C5a receptors.

公开(公告)号：EP1490343A1

公开(公告)日：2004-12-29

申请号：EP03726169.0

申请日：2003-03-28

申请人： Neurogen Corporation

发明人： LUKE, George, P. ,  MAYNARD, George ,  MITCHELL, Scott ,  THURKAUF, Andrew ,  XIE, Linghong ,  ZHANG, LuYan ,  ZHANG, Suoming ,  ZHAO, He ,  CHENARD, Bertrand, L. ,  GAO, Yang ,  HAN, Bingsong ,  HE, Xiao, Shu

IPC分类号： C07D233/54 ,  A61K31/4164

CPC分类号： C07D233/64 ,  A61K31/4164 ,  C07D233/68 ,  C07D235/02 ,  C07D235/30 ,  C07D237/12 ,  C07D401/04 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

摘要： The invention provides Aryl substituted imidazoles, pyrazoles, pyridizines and related compounds of the Formula (I) where the ring system represented by Formula (A) is a 5 membered heteroaryl ring system, in which x is 0, A is chosen from carbon and heteroatoms nitrogen, oxygen, and sulfur, and E and G are independently carbon or nitrogen, provided that the 5 membered heteroaryl ring system does not contain more than 3 heteroatoms or more than 1 oxygen or sulfur atom, or a 6 membered heteroaryl ring system, in which x is 1, A, B, E, and G are independently chosen from carbon and nitrogen, provided that the 6 membered heteroaryl ring system does not contain more than 3 nitrogen atoms. The remaining variables, Ar1, Ar2, R, R1, R2, R3, R4, R5, R6, y and z are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of the invention act bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in treating a variety of inflammatory and immune system disorders.

公开(公告)号：EP1368342A2

公开(公告)日：2003-12-10

申请号：EP01992307.7

申请日：2001-12-21

申请人： NEUROGEN CORPORATION ,  PFIZER INC.

发明人： LI, Guiying ,  PETERSON, John, M. ,  ALBAUGH, Pamela ,  CURRIE, Kevin, S. ,  CAI, Guolin ,  GUSTAVSON, Linda, M. ,  LEE, Kyungae ,  HUTCHISON, Alan ,  SINGH, Vinod ,  MAYNARD, George, D. ,  YUAN, Jun ,  LING HONG, Xie ,  GHOSH, Manuka ,  LIU, Nian ,  LUKE, George, P. ,  MITCHELL, Scott ,  ALLEN, Martin, Patrick ,  LIRAS, Spiros

IPC分类号： C07D401/14 ,  C07D403/06 ,  C07D413/14 ,  C07D403/14 ,  C07D471/04 ,  C07D417/04 ,  C07D403/04 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  A61K31/415 ,  A61P25/00

CPC分类号： C07D401/04 ,  C07D233/20 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D473/00 ,  C07D491/08 ,  C07D491/10

摘要： This invention relates to benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds, all of which may be described by of Formula (I). The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABAA receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Novel processes for preparing compounds of Formula I are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABAA receptors in tissue sections.

公开(公告)号：EP1368342B3

公开(公告)日：2010-12-01

申请号：EP01992307.7

申请日：2001-12-21

申请人： NEUROGEN CORPORATION ,  Pfizer Inc.

发明人： LI, Guiying ,  PETERSON, John, M. ,  ALBAUGH, Pamela ,  CURRIE, Kevin, S. ,  CAI, Guolin ,  GUSTAVSON, Linda, M. ,  LEE, Kyungae ,  HUTCHISON, Alan ,  SINGH, Vinod ,  MAYNARD, George, D. ,  YUAN, Jun ,  LING HONG, Xie ,  GHOSH, Manuka ,  LIU, Nian ,  LUKE, George, P. ,  MITCHELL, Scott ,  ALLEN, Martin, Patrick ,  LIRAS, Spiros

IPC分类号： C07D401/14 ,  C07D403/06 ,  C07D413/14 ,  C07D403/14 ,  C07D471/04 ,  C07D417/04 ,  C07D403/04 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  A61K31/415 ,  A61P25/00

CPC分类号： C07D401/04 ,  C07D233/20 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D473/00 ,  C07D491/08 ,  C07D491/10

摘要： This invention relates to benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds, all of which may be described by of Formula (I). The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABAA receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Novel processes for preparing compounds of Formula I are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABAA receptors in tissue sections.

公开(公告)号：EP1487798A1

公开(公告)日：2004-12-22

申请号：EP03714371.6

申请日：2003-03-25

申请人： Neurogen Corporation

发明人： MITCHELL, Scott ,  OHLIGER, Robert ,  ZHANG, LuYan ,  ZHAO, He ,  CURRIE, Kevin ,  LEE, Kyungae

IPC分类号： C07D217/04 ,  A61K31/47

CPC分类号： C07D221/20 ,  A61K31/47 ,  C07D211/14 ,  C07D211/70 ,  C07D217/04 ,  C07D217/14 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/04 ,  C07D417/12 ,  C07D495/04

摘要： Substituted tetrahydroisoquinolines of Formula I are provided. Such compounds are ligands that may be used to modulate C5a receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological C5a receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

公开(公告)号：EP1406906A1

公开(公告)日：2004-04-14

申请号：EP02749983.9

申请日：2002-07-12

申请人： NEUROGEN CORPORATION

发明人： HUTCHISON, Alan ,  MAYNARD, George ,  ALBAUGH, Pamela ,  XIE, Linghong ,  YUAN, Jun ,  MITCHELL, Scott ,  SINGH, Vinod ,  GHOSH, Manuka ,  LI, Guiying ,  LIU, Nian

IPC分类号： C07D513/04 ,  C07D471/04 ,  C07D487/04 ,  A61K31/437 ,  A61K31/5025 ,  A61K31/519 ,  A61K31/4985 ,  A61P25/00

CPC分类号： C07D487/04 ,  C07D471/04 ,  C07D513/04

摘要： This invention relates to heteroaryl substituted fused bicyclic heteroaryl compounds, such as heteroaryl substituted imidazopyridines, imidazopyrazines, imidazopyridizines, imidazopyrimidines, and imidazothiazoles, which may be described by Formula I or Formula II: The invention is particularly relates to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABAA receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Processes for preparing compounds of Formula I and Formula II are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I or Formula II in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABAA receptors in tissue sections.