公开(公告)号：US07482350B2

公开(公告)日：2009-01-27

申请号：US11123755

申请日：2005-05-06

Applicant: George D. Maynard ,  Manuka Ghosh ,  Jun Yuan ,  Kevin S. Currie ,  Scott Mitchell ,  Qin Guo ,  He Zhao

Inventor： George D. Maynard ,  Manuka Ghosh ,  Jun Yuan ,  Kevin S. Currie ,  Scott Mitchell ,  Qin Guo ,  He Zhao

IPC: A01N43/54 ,  C07D239/42 ,  C07D401/04 ,  C07D403/00

CPC classification number: 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

Abstract: 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 agonist 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.

Abstract translation: 提供式I和式II的4,5-二取代-2-芳基嘧啶：其中R1，R2，R3，R8，R9，A和Ar如本文所定义。 这些化合物是C5a受体的配体。 优选的式I和II化合物以高亲和力结合C5a受体，并在C5a受体上呈现中性拮抗剂或反向激动剂活性。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物在治疗各种炎性，心血管和免疫系统疾病中的用途。 此外，本发明提供标记的4,5-二取代-2-芳基嘧啶，其可用作C5a受体定位的探针。

公开(公告)号：US20080267887A1

公开(公告)日：2008-10-30

申请号：US11664565

申请日：2005-10-05

Applicant: Jun Yuan ,  Peter Hrnciar ,  Qin Guo ,  George D. Maynard

Inventor： Jun Yuan ,  Peter Hrnciar ,  Qin Guo ,  George D. Maynard

IPC: A61K9/12 ,  C07D471/04 ,  A61K31/437 ,  C07K14/705 ,  A61P9/10 ,  C12Q1/02 ,  C12N5/06 ,  A61K31/506

CPC classification number: C07D471/04

Abstract: Pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds analogues of the formula: wherein R, R2, R5, E, Z1, Z3, Z4, and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds of the invention 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 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 pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds, which are useful as probes for the localization of C5a receptors.

Abstract translation: 吡咯并 - 吡啶，吡咯并 - 嘧啶和相关杂环化合物，其分子式如下：其中R 1，R 2，R 5，E，Z 1， Z 3，Z 4和Ar如本文所定义。 这些化合物是C5a受体的配体。 本发明优选的吡咯并 - 吡啶，吡咯并 - 嘧啶和相关杂环化合物以高亲和力结合C5a受体，并在C5a受体上表现出中性拮抗剂或反向激动剂活性。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物在治疗各种炎性，心血管和免疫系统疾病中的用途。 此外，本发明提供了标记的吡咯并 - 吡啶，吡咯并 - 嘧啶和相关杂环化合物，其可用作C5a受体定位的探针。

公开(公告)号：US07342115B2

公开(公告)日：2008-03-11

申请号：US10704364

申请日：2003-11-07

Applicant: Alan J. Hutchison ,  Jun Yuan ,  Kyungae Lee ,  George D. Maynard ,  Bertrand L. Chenard ,  Nian Liu ,  Qin Guo ,  Zihong Guo ,  Peter Hrnciar

Inventor： Alan J. Hutchison ,  Jun Yuan ,  Kyungae Lee ,  George D. Maynard ,  Bertrand L. Chenard ,  Nian Liu ,  Qin Guo ,  Zihong Guo ,  Peter Hrnciar

IPC: C07D213/61 ,  C07D213/62 ,  C07D213/72 ,  C07D213/73 ,  C07D213/84

CPC classification number: C07D213/30 ,  C07B2200/05 ,  C07D213/38 ,  C07D213/42 ,  C07D213/64 ,  C07D213/65 ,  C07D213/68 ,  C07D213/71 ,  C07D213/74 ,  C07D213/81 ,  C07D213/84 ,  C07D213/89 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C40B40/00

Abstract: 3-substituted-6-aryl pyridines of Formula I are provided: wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptor. Preferred compounds of Formula I 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 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 3-substituted-6-aryl pyridines, which are useful as probes for the localization of C5a receptors.

Abstract translation: 提供式I的3-取代-6-芳基吡啶：其中R 1，R 2，R 3，R 8 R 9，R 9，A和Ar如本文所定义。 这些化合物是C5a受体的配体。 优选的式I化合物以高亲和力结合C5a受体，并在C5a受体上呈现中性拮抗剂或反向激动剂活性。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物在治疗各种炎性，心血管和免疫系统疾病中的用途。 此外，本发明提供标记的3-取代-6-芳基吡啶，其可用作C5a受体定位的探针。

公开(公告)号：US07300945B2

公开(公告)日：2007-11-27

申请号：US11179458

申请日：2005-07-12

Applicant: Guiying Li ,  Pamela Albaugh ,  Kevin S. Currie ,  Guolin Cai ,  Linda M. Gustavson ,  Kyungae Lee ,  Alan Hutchison ,  George D. Maynard ,  Jun Yuan ,  Ling Hong Xie ,  Manuka Ghosh ,  Nian Liu ,  George P. Luke ,  Scott Mitchell ,  Martin Patrick Allen ,  Spiros Liras

Inventor： Guiying Li ,  Pamela Albaugh ,  Kevin S. Currie ,  Guolin Cai ,  Linda M. Gustavson ,  Kyungae Lee ,  Alan Hutchison ,  George D. Maynard ,  Jun Yuan ,  Ling Hong Xie ,  Manuka Ghosh ,  Nian Liu ,  George P. Luke ,  Scott Mitchell ,  Martin Patrick Allen ,  Spiros Liras

IPC: C07D471/04 ,  A61K31/437

CPC classification number: 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

Abstract: 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.

Abstract translation: 本发明涉及苯并咪唑，吡啶基咪唑和相关双环杂芳基化合物，所有这些可以由式I描述。本发明特别涉及以高选择性和高亲和力结合GABA A的苯并二氮杂部位的化合物， / SUB>受体。 本发明还涉及包含这些化合物的药物组合物以及这些化合物在治疗某些中枢神经系统（CNS）疾病中的用途。 公开了制备式I化合物的新方法。 本发明还涉及式I的苯并咪唑，吡啶基咪唑和相关的双环杂芳基化合物与一种或多种其它CNS剂的组合用于增强其它CNS剂的作用。 此外，本发明涉及使用这些化合物作为组织切片中GABA A A受体定位的探针。

公开(公告)号：US06413982B1

公开(公告)日：2002-07-02

申请号：US09536922

申请日：2000-03-28

Applicant: Jun Yuan ,  George D. Maynard ,  Alan Hutchison ,  Stanislaw Rachwal

Inventor： Jun Yuan ,  George D. Maynard ,  Alan Hutchison ,  Stanislaw Rachwal

IPC: A61L3147

CPC classification number: C07D401/04 ,  C07D401/14 ,  C07D413/04 ,  C07D487/04 ,  G01N33/9426 ,  G01N2333/70571

Abstract: Disclosed are compounds of the Formula where R1, R2, R3, R4, X, Y1, and Y2 are defined herein. These compounds bind with high affinity to NK-3 receptors and/or GABAA receptors. Also provided are pharmaceutical compositions comprising these compounds, and methods of treating patients suffering from various central nervous system and peripheral diseases or disorders with these pharmaceutical compositions. This invention also relates to the use of such compounds in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. The compounds of this invention are also useful as probes for the localization of NK-3 receptors and GABAA receptors.

Abstract translation: 公开了本文定义的化学式R 1，R 2，R 3，R 4，X，Y 1和Y 2的化合物。 这些化合物以高亲和力结合NK-3受体和/或GABA A受体。 还提供了包含这些化合物的药物组合物，以及用这些药物组合物治疗患有各种中枢神经系统和外周疾病或病症的患者的方法。 本发明还涉及这样的化合物与一种或多种其它CNS剂组合用于增强其它CNS剂的作用的用途。 本发明的化合物也可用作NK-3受体和GABA A受体定位的探针。

公开(公告)号：US06316445B1

公开(公告)日：2001-11-13

申请号：US09648005

申请日：1999-05-06

Applicant: Timothy P. Burkholder ,  George D. Maynard ,  Elizabeth M. Kudlacz

Inventor： Timothy P. Burkholder ,  George D. Maynard ,  Elizabeth M. Kudlacz

IPC: C07D40114

CPC classification number: C07D401/06 ,  C07D211/64 ,  C07D401/12 ,  C07D401/14 ,  C07D409/06

Abstract: The present invention relates to novel carboxy substituted acyclic carboxamide derivatives of formula (1)): and stereoisomers and pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, cough, and bronchitis.

Abstract translation: 本发明涉及式（1））的新的羧基取代的无环羧酰胺衍生物：及其立体异构体及其药学上可接受的盐及其作为速激肽受体拮抗剂的用途。 这样的拮抗剂可用于治疗速激肽介导的疾病和本文公开的病症，包括：哮喘，咳嗽和支气管炎。

公开(公告)号：US06221875B1

公开(公告)日：2001-04-24

申请号：US09283534

申请日：1999-04-01

Applicant: James W. Darrow ,  George D. Maynard ,  Raymond F. Horvath ,  Jennifer Tran ,  Stephane De Lombaert

Inventor： James W. Darrow ,  George D. Maynard ,  Raymond F. Horvath ,  Jennifer Tran ,  Stephane De Lombaert

IPC: A61K31437

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: Disclosed are compounds of the formula: wherein Ar, R1, W and X are substituents as defined herein, which compounds are effective neuropeptide Y1 receptor antagonists, and are therefore useful in the treatment of a wide variety of clinical conditions which are characterized by the presence of an excess of neuropeptide Y.

Abstract translation: 公开的是下式的化合物：其中Ar，R 1，W和X是如本文所定义的取代基，这些化合物是有效的神经肽Y1受体拮抗剂，因此可用于治疗各种临床病症，其特征在于存在 的过量的神经肽Y.

公开(公告)号：US5977139A

公开(公告)日：1999-11-02

申请号：US971891

申请日：1997-11-17

Applicant: Timothy P. Burkholder ,  George D. Maynard ,  Elizabeth M. Kudlacz

Inventor： Timothy P. Burkholder ,  George D. Maynard ,  Elizabeth M. Kudlacz

IPC: C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  A01N43/40

CPC classification number: C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14

Abstract: The present invention relates to novel carboxy substituted cyclic carboxamide derivatives of formula (1), ##STR1## and stereoisomers and pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, coughs and bronchitis.

Abstract translation: 本发明涉及式（1）的新的羧基取代的环状甲酰胺衍生物及其立体异构体和药学上可接受的盐，以及它们作为速激肽受体拮抗剂的用途。 这样的拮抗剂可用于治疗速激肽介导的疾病和本文公开的病症，包括：哮喘，咳嗽和支气管炎。

公开(公告)号：US5739150A

公开(公告)日：1998-04-14

申请号：US457199

申请日：1995-06-01

Applicant: Albert A. Carr ,  John M. Kane ,  George D. Maynard ,  Hsien C. Cheng ,  Mark W. Dudley

Inventor： Albert A. Carr ,  John M. Kane ,  George D. Maynard ,  Hsien C. Cheng ,  Mark W. Dudley

IPC: A61K31/4433 ,  A61K31/445 ,  A61K31/454 ,  A61P37/08 ,  C07D409/06 ,  C07D409/14 ,  C07D417/06 ,  C07D417/14 ,  C07D409/02 ,  C07D417/02

CPC classification number: C07D409/06 ,  C07D409/14 ,  C07D417/06 ,  C07D417/14

Abstract: Piperidinyl thiacyclic derivatives useful in the treatment of allergic diseases and diseases responding to antagonism of 5HT.sub.2 receptors, pharmaceutical compositions and a methods of treatment using these compounds.

Abstract translation: 可用于治疗过敏性疾病和对5HT2受体拮抗作用的疾病的哌啶基硫辛酸衍生物，药物组合物和使用这些化合物的治疗方法。

公开(公告)号：US5596003A

公开(公告)日：1997-01-21

申请号：US457901

申请日：1995-06-01

Applicant: Albert A. Carr ,  John M. Kane ,  George D. Maynard ,  Hsien C. Cheng ,  Mark W. Dudley

Inventor： Albert A. Carr ,  John M. Kane ,  George D. Maynard ,  Hsien C. Cheng ,  Mark W. Dudley

IPC: A61K31/4433 ,  A61K31/445 ,  A61K31/454 ,  A61P37/08 ,  C07D409/06 ,  C07D409/14 ,  C07D417/06 ,  C07D417/14 ,  C07D417/02

CPC classification number: C07D409/06 ,  C07D409/14 ,  C07D417/06 ,  C07D417/14

Abstract: Piperidinyl thiacyclic derivatives useful in the treatment of allergic diseases and diseases responding to antagonism of 5HT.sub.2 receptors, pharmaceutical compositions and a methods of treatment using these compounds.