公开(公告)号：EP1322309B1

公开(公告)日：2008-08-13

申请号：EP00965522.6

申请日：2000-09-29

申请人： NEUROGEN CORPORATION

发明人： THURKAUF, Andrew ,  ZHANG, Xiaoyan ,  HE, Xia-shu ,  ZHAO, He ,  PETERSON, John ,  MAYNARD, George ,  OHLIGER, Robert

IPC分类号： C07D405/12 ,  C07D233/54 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D401/12 ,  A61K31/38 ,  A61K31/40 ,  A61K31/44 ,  A61K31/415 ,  A61K31/47

CPC分类号： C07D207/327 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/44 ,  A61K31/47 ,  C07D217/04 ,  C07D231/12 ,  C07D233/56 ,  C07D233/64 ,  C07D249/08 ,  C07D333/24 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D471/04

摘要： The invention includes low molecular weight, non-peptidic, non-peptidommetic, organic molecules that can act as modulators of mammalian complement C5a receptors, preferably ones that act as high affinity C5a receptor ligands and also such ligands that can act as antagonists or inverse agonists of complement C5a receptors. Preferred compounds of the invention possess some or all of the following properties in that they are: 1) multi-aryl in structure; 2) heteroaryl in structure; 3) a pharmaceutically acceptable oral dose can provide a detectable in vivo effect; 4) comprise fewer than four or preferably no amide bonds, and 5) capable of habiting leukocyte chemotaxis at nanomolar or sub-nanomolar concentrations. The invention also includes pharmaceutical composition comprising such compounds and the use of such compounds in treating a variety of inflammatory and immune system disorders.

公开(公告)号：EP1322309A2

公开(公告)日：2003-07-02

申请号：EP00965522.6

申请日：2000-09-29

申请人： Neurogen Corporation

发明人： THURKAUF, Andrew ,  ZHANG, Xiaoyan ,  HE, Xia-shu ,  ZHAO, He ,  PETERSON, John ,  MAYNARD, George ,  OHLIGER, Robert

IPC分类号： A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/44 ,  A61K31/47 ,  C07D215/00 ,  C07D233/02 ,  C07D235/02 ,  C07D317/44 ,  C07D405/00 ,  C07D419/00 ,  C07D471/02

CPC分类号： C07D207/327 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/44 ,  A61K31/47 ,  C07D217/04 ,  C07D231/12 ,  C07D233/56 ,  C07D233/64 ,  C07D249/08 ,  C07D333/24 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D471/04

摘要： The invention includes low molecular weight, non-peptidic, non-peptidommetic, organic molecules that can act as modulators of mammalian complement C5a receptors, preferably ones that act as high affinity C5a receptor ligands and also such ligands that can act as antagonists or inverse agonists of complement C5a receptors. Preferred compounds of the invention possess some or all of the following properties in that they are: 1) multi-aryl in structure; 2) heteroaryl in structure; 3) a pharmaceutically acceptable oral dose can provide a detectable in vivo effect; 4) comprise fewer than four or preferably no amide bonds, and 5) capable of habiting leukocyte chemotaxis at nanomolar or sub-nanomolar concentrations. The invention also includes pharmaceutical composition comprising such compounds and the use of such compounds in treating a variety of inflammatory and immune system disorders.

公开(公告)号：EP1487796A1

公开(公告)日：2004-12-22

申请号：EP03745585.4

申请日：2003-03-25

申请人： NEUROGEN CORPORATION

发明人： GAO, Yang ,  HUTCHISON, Alan ,  PETERSON, John ,  PRINGLE, Wallace ,  THURKAUF, Andrew ,  YOON, Taeyoung ,  ZHAO, He

IPC分类号： C07D215/00 ,  C07D233/02 ,  C07D235/02 ,  C07D317/44 ,  C07D405/00 ,  C07D409/00 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415

CPC分类号： C07D249/08 ,  C07C233/65 ,  C07C235/62 ,  C07C2602/08 ,  C07D207/327 ,  C07D209/08 ,  C07D231/12 ,  C07D231/56 ,  C07D233/56 ,  C07D235/06 ,  C07D317/58 ,  C07D333/24

摘要： Substituted biaryl amides 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.

摘要翻译： 提供式I的取代的联芳基酰胺。 这些化合物是可用于在体内或体外调节C5a受体活性的配体，并且特别可用于治疗与人类，驯养伴侣动物和家畜中的病理性C5a受体激活相关的病症。 提供了用于治疗这些疾病的药物组合物和方法，以及使用这些配体进行受体定位研究的方法。

公开(公告)号：EP0793653A1

公开(公告)日：1997-09-10

申请号：EP95942473.0

申请日：1995-11-22

申请人： NEUROGEN CORPORATION

发明人： THURKAUF, Andrew ,  HORVATH, Raymond, F. ,  YUAN, Jun ,  PETERSON, John, M.

IPC分类号： C07D233 ,  A61K31 ,  A61P25 ,  A61P43 ,  C07D401 ,  C07D403 ,  C07D487

CPC分类号： C07D233/64 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

摘要： Disclosed are compounds of formula (III), wherein R1 represents optionally substituted aryl, heteroaryl, arylalkyl, or cycloalkyl groups; X, Z, and Y are optionally substituted nitrogen or carbon atoms; R3 and R4 are organic or inorganic substituents which may together form ring structures; m is zero, one or two; and R5 and R6 are organic or inorganic substituents; and the pharmaceutically acceptable addition salts thereof, which compounds are highly selective partial agonists or antagonists at brain dopamine receptor subtypes or prodrugs thereof and are useful in the diagnosis and treatment of affective disorders such as schizophrenia and depression as well as certain movement disorders such as Parkinsonism.

公开(公告)号：EP0552237A1

公开(公告)日：1993-07-28

申请号：EP91918267.0

申请日：1991-10-08

申请人： NEUROGEN CORPORATION

发明人： THURKAUF, Andrew ,  HUTCHISON, Alan ,  SINGH, Vinod 211 East Main Street

IPC分类号： A61K31 ,  A61P25 ,  A61P39 ,  A61P43 ,  C07D471 ,  C07D487 ,  C07D491

CPC分类号： C07D471/14 ,  C07D487/04

摘要： Cette invention se rapporte à des composés de la formule (I) et à des sels non-toxiques pharmaceutiquement acceptables de ces composés, où n vaut 0, 1 ou 2, et R1, R2, X, Y et W sont des variables. Ces composés sont des agonistes, des antagonistes ou des agonistes inverses hautement sélectifs de récepteurs de GABAa dans le cerveau ou de précurseurs de ceux-ci, et sont utiles dans le diagnostic et le traitement de l'anxiété, du sommeil, de troubles dus à des attaques, d'overdose de drogues du type benzodiazépine, et dans l'amélioration de la capacité de réaction mentale.

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：EP1068193A1

公开(公告)日：2001-01-17

申请号：EP99909657.1

申请日：1999-02-26

申请人： NEUROGEN CORPORATION

发明人： KOVER, Renata, X. ,  TERDJANIAN, Silva ,  TRAN, Jennifer ,  THURKAUF, Andrew

IPC分类号： C07D401/06 ,  A61K31/445 ,  C07D295/14 ,  A61K31/495 ,  C07D209/08 ,  C07D215/08 ,  C07D265/36 ,  A61K31/535 ,  C07D279/16 ,  A61K31/54 ,  C07D209/54

CPC分类号： C07D295/15 ,  C07D209/08 ,  C07D209/54 ,  C07D215/08 ,  C07D265/36 ,  C07D279/16 ,  C07D401/06

摘要： Disclosed are compounds of formula (I) or pharmaceutically acceptable addition salts thereof wherein: Y represents oxygen or sulfur; Z is nitrogen or CH; R1, R2 and R3 represents hydrogen, halogen, hydroxy, alkoxy, alkyl, trifluoromethyl or trifluoromethoxy; R4 and R4' represent hydrogen, alkyl or form a ring with the atom to which they are attached; R5 represents hydrogen, alkyl, alkoxy, or alkylthio, and R6 represents hydrogen or alkyl; or R5 and R6 form a ring together with the atoms to which they are attached; and R7, R8, R9, R10 and R11 represent hydrogen or alkyl, which compounds are useful for the treatment and/or prevention of neuropsychological disorders including, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents. Also encompassed within the scope of the invention are intermediates of formulae (VII-a) and (VII-b) wherein X represents oxygen, or sulfur, or CH2, m is zero or an integer of from 1-4, and L is a leaving group.

公开(公告)号：EP0639275A1

公开(公告)日：1995-02-22

申请号：EP93910819.0

申请日：1993-04-30

申请人： NEUROGEN CORPORATION

发明人： SHAW, Kenneth ,  HUTCHISON, Alan ,  THURKAUF, Andrew ,  TALLMAN, John

IPC分类号： G01N33 ,  A61K31 ,  A61P25 ,  C07B59 ,  C07D487

CPC分类号： G01N33/9426 ,  C07B59/002 ,  G01N33/566 ,  G01N33/948 ,  G01N2500/20

公开(公告)号：EP0960106B1

公开(公告)日：2004-05-06

申请号：EP98903796.5

申请日：1998-01-29

申请人： NEUROGEN CORPORATION

发明人： THURKAUF, Andrew ,  CHEN, Xi

IPC分类号： C07D295/06 ,  A61K31/495 ,  C07D405/10

CPC分类号： C07D295/073 ,  A61K31/495 ,  C07C2603/08 ,  C07D295/096 ,  C07D295/112 ,  C07D295/135

摘要： Disclosed are compounds of formula (I) or the pharmaceutically acceptable addition salts thereof wherein: R1 is halogen or C1-C4 alkyl; and R2 and R3 are the same or different and represent hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, alkylthio, hydroxy, amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino, or R2 and R3 together represent a 4 carbon alkenylene moiety that together with the phenyl ring to which they are attached form a naphthyl moiety, which compounds are dopamine D4(ant)agonists and useful in the treatment of neuropsychological diseases such as schizophrenia, psychotic depression and mania.

公开(公告)号：EP1140879A1

公开(公告)日：2001-10-10

申请号：EP00905545.0

申请日：2000-01-06

申请人： NEUROGEN CORPORATION

发明人： ZHANG, Xiaoyan ,  TRAN, Jennifer ,  ZHAO, He ,  THURKAUF, Andrew

IPC分类号： C07D295/06 ,  C07D295/02 ,  C07D295/12 ,  A61K31/495 ,  A61P25/00

CPC分类号： C07D295/03 ,  C07D295/073 ,  C07D295/135

摘要： Disclosed are compounds of formula (I) or pharmaceutically acceptable addition salts thereof wherein: R1, R2, R3, R4 and R5, R6, R7 and R8 represent organic and/or inorganic substituents as defined herein, which compounds are useful for the treatment and/or prevention of neuropsychological disorders including, but not limited to, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents.