公开(公告)号：US09452161B2

公开(公告)日：2016-09-27

申请号：US15016528

申请日：2016-02-05

Applicant: Mathai Mammen ,  YuHua Ji ,  YongQi Mu ,  Craig Husfeld ,  Li Li

Inventor： Mathai Mammen ,  YuHua Ji ,  YongQi Mu ,  Craig Husfeld ,  Li Li

IPC: C07D401/00 ,  A61K31/44 ,  A61K31/4545 ,  A61K9/16 ,  A61K45/06

CPC classification number: C07D211/62 ,  A61K9/124 ,  A61K9/1623 ,  A61K9/1652 ,  A61K31/4545 ,  A61K45/06 ,  C07D401/12

Abstract: This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, s, t, W, Ar1, R1, R2, R3, R4, R6, R7, and R8 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

公开(公告)号：US08618131B2

公开(公告)日：2013-12-31

申请号：US13545523

申请日：2012-07-10

Applicant: Mathai Mammen ,  Sarah Dunham ,  Adam D. Hughes ,  Craig Husfeld ,  Eric L. Stangeland

Inventor： Mathai Mammen ,  Sarah Dunham ,  Adam D. Hughes ,  Craig Husfeld ,  Eric L. Stangeland

IPC: A61K31/47 ,  C07D215/00

CPC classification number: C07D211/46 ,  A61K31/445 ,  A61K31/452 ,  C07D211/48 ,  C07D211/58 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/06 ,  C07D409/12 ,  C07D453/02 ,  C07D471/08 ,  G01N33/9433

Abstract: This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthmas.

Abstract translation: 本发明提供式I的联苯衍生物：其中R1，R2，R3，R4，R5，R6，R7，W，a，b和c如说明书中所定义，或其药学上可接受的盐或溶剂合物或立体异构体。 本发明的联苯衍生物具有β2肾上腺素能受体激动剂和毒蕈碱受体拮抗剂活性，因此，这种联苯衍生物可用于治疗肺部疾病，如慢性阻塞性肺病和哮喘。

公开(公告)号：US20130323271A1

公开(公告)日：2013-12-05

申请号：US13905338

申请日：2013-05-30

Applicant: Mathai Mammen ,  Adam D. Hughes

Inventor： Mathai Mammen ,  Adam D. Hughes

IPC: C07C233/56 ,  A61K31/42 ,  C07D271/04 ,  C07D413/12 ,  A61K31/4245 ,  A61K31/216 ,  C07D261/18 ,  A61K45/06

CPC classification number: C07D271/08 ,  A61K31/216 ,  A61K31/42 ,  A61K31/4245 ,  A61K45/06 ,  C07C233/56 ,  C07C235/80 ,  C07C243/28 ,  C07D261/18 ,  C07D271/04 ,  C07D413/12

Abstract: In one aspect, the invention relates to compounds having the formula: where R1, R2, R3, R7, R8, Z, X, b, and c are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds are nitric oxide donors and have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Abstract translation: 一方面，本发明涉及具有下式的化合物：其中R1，R2，R3，R7，R8，Z，X，b和c如说明书中所定义，或其药学上可接受的盐。 这些化合物是一氧化氮供体并且具有去甲肾上腺素抑制活性。 另一方面，本发明涉及包含这些化合物的药物组合物; 使用这些化合物的方法; 以及制备这些化合物的方法和中间体。

公开(公告)号：US08067439B2

公开(公告)日：2011-11-29

申请号：US12938539

申请日：2010-11-03

Applicant: Mathai Mammen ,  YuHua Ji ,  YongQi Mu ,  Eric L. Stangeland ,  Aaron Kushner ,  Craig Husfeld

Inventor： Mathai Mammen ,  YuHua Ji ,  YongQi Mu ,  Eric L. Stangeland ,  Aaron Kushner ,  Craig Husfeld

IPC: C07D401/12 ,  A61K31/4465 ,  A61K31/4523

CPC classification number: C07D211/62 ,  C07D211/60

Abstract: This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, r, R1, R2, R3, R4, R5, R6, R7, and W are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

Abstract translation: 本发明提供式I化合物：其中a，b，c，d，m，n，p，r，R1，R2，R3，R4，R5，R6，R7和W如说明书中所定义。 式I化合物是毒蕈碱受体拮抗剂。 本发明还提供含有这些化合物的药物组合物，用于制备这些化合物的方法和中间体以及使用这些化合物治疗肺部疾病的方法。

公开(公告)号：US08030502B2

公开(公告)日：2011-10-04

申请号：US11974982

申请日：2007-10-17

Applicant: Mathai Mammen ,  David Oare ,  Junning Lee ,  Weijiang Zhang

Inventor： Mathai Mammen ,  David Oare ,  Junning Lee ,  Weijiang Zhang

IPC: C07D207/08

CPC classification number: C07D401/14

Abstract: This invention provides 4-amino-1-(pyridylmethyl)piperidine and related compounds and pharmaceutically acceptable salts thereof which are useful as muscarinic receptor antagonists. This invention also provides pharmaceutical compositions containing such compounds; processes and intermediates useful for preparing such compounds; and methods for treating disease conditions mediated by muscarinic receptors, such as overactive bladder, irritable bowel syndrome and chronic obstructive pulmonary disease, using such compounds.

Abstract translation: 本发明提供了可用作毒蕈碱受体拮抗剂的4-氨基-1-（吡啶基甲基）哌啶及其相关化合物及其药学上可接受的盐。 本发明还提供含有这些化合物的药物组合物; 用于制备这些化合物的方法和中间体; 以及使用这些化合物治疗由毒蕈碱受体介导的疾病状况的方法，例如膀胱过度活动，肠易激综合征和慢性阻塞性肺疾病。

公开(公告)号：US08017783B2

公开(公告)日：2011-09-13

申请号：US11899181

申请日：2007-09-05

Applicant: Mathai Mammen ,  Yu-Hua Ji ,  YongQi Mu ,  Craig Husfeld ,  Li Li

Inventor： Mathai Mammen ,  Yu-Hua Ji ,  YongQi Mu ,  Craig Husfeld ,  Li Li

IPC: C07D401/12

CPC classification number: C07D211/62 ,  A61K9/124 ,  A61K9/1623 ,  A61K9/1652 ,  A61K31/4545 ,  A61K45/06 ,  C07D401/12

Abstract: This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, s, t, W, Ar1, R1, R2, R3, R4, R6, R7, and R8 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

公开(公告)号：US07879879B2

公开(公告)日：2011-02-01

申请号：US11448317

申请日：2006-06-07

Applicant: Mathai Mammen ,  Sarah Dunham ,  Adam Hughes ,  Craig Husfeld ,  Eric Stangeland ,  Yan Chen

Inventor： Mathai Mammen ,  Sarah Dunham ,  Adam Hughes ,  Craig Husfeld ,  Eric Stangeland ,  Yan Chen

IPC: A61K31/445 ,  C07D211/54 ,  C07D211/56

CPC classification number: C07D211/46 ,  A61K31/445 ,  A61K31/452 ,  C07D211/48 ,  C07D211/58 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/06 ,  C07D409/12 ,  C07D453/02 ,  C07D471/08 ,  G01N33/9433

Abstract: This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

Abstract translation: 本发明提供式I的联苯衍生物：其中R1，R2，R3，R4，R5，R6，R7，W，a，b和c如说明书中所定义，或其药学上可接受的盐或溶剂合物或立体异构体。 本发明的联苯衍生物具有二肾上腺素能受体激动剂和毒蕈碱受体拮抗剂活性，因此，这种联苯衍生物可用于治疗肺部疾病，如慢性阻塞性肺疾病和哮喘。

公开(公告)号：US07858792B2

公开(公告)日：2010-12-28

申请号：US12402665

申请日：2009-03-12

Applicant: Mathai Mammen ,  Yu-Hua Ji ,  YongQi Mu ,  Viengkham Malathong

Inventor： Mathai Mammen ,  Yu-Hua Ji ,  YongQi Mu ,  Viengkham Malathong

IPC: C07D215/02 ,  C07D217/02 ,  A61K31/47

CPC classification number: C07D211/46 ,  C07D211/60 ,  C07D211/62 ,  C07D401/12 ,  C07D405/12

Abstract: This invention provides compounds of formula I: wherein a, b, c, m, p, r, R1, R2, R3, R4, R5, R6, W and X1 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

Abstract translation: 本发明提供式I化合物：其中a，b，c，m，p，r，R1，R2，R3，R4，R5，R6，W和X1如说明书中所定义。 式I化合物是毒蕈碱受体拮抗剂。 本发明还提供含有这些化合物的药物组合物，用于制备这些化合物的方法和中间体以及使用这些化合物治疗肺部疾病的方法。

公开(公告)号：US07851632B2

公开(公告)日：2010-12-14

申请号：US11880048

申请日：2007-07-19

Applicant: Mathai Mammen ,  Yu-Hua Ji ,  YongQi Mu ,  Craig Husfeld ,  Li Li

Inventor： Mathai Mammen ,  Yu-Hua Ji ,  YongQi Mu ,  Craig Husfeld ,  Li Li

IPC: A61K31/05 ,  C07D411/08

CPC classification number: C07D211/46 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12

Abstract: This invention provides compounds of formula I: wherein a, b, c, m, p, s, t, W, Ar1, X1, R1, R2, R3, R4, R6, and R7 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

Abstract translation: 本发明提供式I化合物：其中a，b，c，m，p，s，t，W，Ar1，X1，R1，R2，R3，R4，R6和R7如说明书中所定义。 式I化合物是毒蕈碱受体拮抗剂。 本发明还提供含有这些化合物的药物组合物，用于制备这些化合物的方法和中间体以及使用这些化合物治疗肺部疾病的方法。

公开(公告)号：US07851631B2

公开(公告)日：2010-12-14

申请号：US11879829

申请日：2007-07-19

Applicant: Mathai Mammen ,  Yu-Hua Ji ,  YongQi Mu ,  Eric L. Stangeland ,  Aaron Kushner ,  Craig Husfeld

Inventor： Mathai Mammen ,  Yu-Hua Ji ,  YongQi Mu ,  Eric L. Stangeland ,  Aaron Kushner ,  Craig Husfeld

IPC: C07D401/12 ,  A61K31/454

CPC classification number: C07D211/62 ,  C07D211/60

Abstract: This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, r, R1, R2, R3, R4, R5, R6, R7, and W are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.