公开(公告)号：US07368463B2

公开(公告)日：2008-05-06

申请号：US10888855

申请日：2004-07-09

Applicant: Mathai Mammen ,  Richard Wilson ,  Sarah Dunham ,  Adam Hughes ,  Craig Husfeld ,  Yu-Hua Ji ,  Li Li ,  Trevor Mischki ,  Ioanna Stergiades ,  David Oare

Inventor： Mathai Mammen ,  Richard Wilson ,  Sarah Dunham ,  Adam Hughes ,  Craig Husfeld ,  Yu-Hua Ji ,  Li Li ,  Trevor Mischki ,  Ioanna Stergiades ,  David Oare

IPC: A61K31/445 ,  C07D401/12

CPC classification number: C07D401/12 ,  C07D401/14 ,  C07D405/14

Abstract: This invention provides 4-amino-1-benzylpiperidine 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, asthma 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-苄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态如膀胱过度活动症，肠易激综合征，哮喘和慢性阻塞性肺病的方法。

公开(公告)号：US07358244B2

公开(公告)日：2008-04-15

申请号：US10854829

申请日：2004-05-27

Applicant: Mathai Mammen ,  Adam Hughes

Inventor： Mathai Mammen ,  Adam Hughes

IPC: A61K31/44 ,  A61K31/54 ,  C07D221/22 ,  C07D451/02 ,  C07D417/00

CPC classification number: C07D451/02 ,  A61K31/46 ,  A61K31/4743 ,  C07D451/12 ,  C07D471/08

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

Abstract translation: 本发明提供了式I化合物：其中R 1，R 2，R 3，R 4，R 4， 其中R 6，R 6和R 7如本说明书中所定义，或其药学上可接受的盐或溶剂合物或立体异构体。 本发明的化合物具有β2 N 2肾上腺素能受体激动剂和毒蕈碱受体拮抗剂活性。 这些化合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：US07351718B2

公开(公告)日：2008-04-01

申请号：US11602802

申请日：2006-11-21

Applicant: Mathai Mammen ,  Adam Hughes ,  Yu-hua Ji ,  Li Li ,  Weijiang Zhang

Inventor： Mathai Mammen ,  Adam Hughes ,  Yu-hua Ji ,  Li Li ,  Weijiang Zhang

IPC: A61K31/40 ,  A61K31/445 ,  C07D207/04 ,  C07D211/06

CPC classification number: C07D207/08 ,  A61K31/40 ,  C07D207/09 ,  C07D207/16 ,  C07D211/34

Abstract: This invention is directed to compounds of formula I: wherein R1-R5 and a-e are as defined in the specification; or pharmaceutically-acceptable salt or solvate or stereoisomer thereof. The invention also directed to pharmaceutical compositions containing such compounds; processes and intermediates useful for preparing such compounds; and methods for treating disease conditions mediated by muscarinic receptors using such compounds.

公开(公告)号：US20080071088A1

公开(公告)日：2008-03-20

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：US20080015220A1

公开(公告)日：2008-01-17

申请号：US11888526

申请日：2007-08-01

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

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

IPC: A61K31/47 ,  A61P11/06 ,  A61P9/00

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 asthma.

公开(公告)号：US07265133B2

公开(公告)日：2007-09-04

申请号：US11076796

申请日：2005-03-10

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: C07D211/18 ,  C07D401/12 ,  C07D451/02 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545

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 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，Ar 1，X 1，R 1 R 2，R 3，R 3，R 4，R 6和R 6， 7 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：US20070154948A1

公开(公告)日：2007-07-05

申请号：US11603286

申请日：2006-11-21

Applicant: Burton Christensen ,  Edmund Moran ,  John Griffin ,  J. Judice ,  YongQi Mu ,  John Pace ,  Mathai Mammen ,  James Aggen

Inventor： Burton Christensen ,  Edmund Moran ,  John Griffin ,  J. Judice ,  YongQi Mu ,  John Pace ,  Mathai Mammen ,  James Aggen

IPC: A61K31/545 ,  A61K38/16 ,  A61K31/43 ,  C07D499/44 ,  C07D487/04

CPC classification number: C07D477/12 ,  C07D499/32 ,  C07D499/44 ,  C07D501/56

Abstract: This invention relates to novel multibinding compounds (agents) that are antibacterial agents. The multibinding compounds of the invention comprise from 2-10 ligands covalently connected by a linker or linkers, wherein each of said ligands in their monovalent (i.e., unlinked) state have the ability to bind to a an enzyme involved in cell wall biosynthesis and metabolism, a precursor used in the synthesis of the bacterial cell wall and/or the bacterial cell surface thereby interfere with the synthesis and/or metabolism of the cell wall. In particular the multibinding compounds of the invention comprise from 2-10 ligands covalently connected by a linker or linkers, wherein each of said ligands has a ligand domain capable of binding to penicillin binding proteins, a transpeptidase enzyme, a substrate of a transpeptidase enzyme, a beta-lactamase enzyme, pencillinase enzyme, cephalosporinase enzyme, a transglycoslase enzyme, or a transglycosylase enzyme substrate; Preferably, the ligands are selected from the beta lactam or glycopeptide class of antibacterial agents.

公开(公告)号：US20070135482A1

公开(公告)日：2007-06-14

申请号：US11602703

申请日：2006-11-21

Applicant: Mathai Mammen ,  Adam Hughes ,  Yu-hua Ji ,  Li Li ,  Weijiang Zhang

Inventor： Mathai Mammen ,  Adam Hughes ,  Yu-hua Ji ,  Li Li ,  Weijiang Zhang

IPC: A61K31/445 ,  A61K31/40 ,  C07D211/26 ,  C07D207/30

CPC classification number: C07D207/08 ,  A61K31/40 ,  C07D207/09 ,  C07D207/16 ,  C07D211/34

Abstract: This invention is directed to compounds of formula I: wherein R1-R5 and a-e are as defined in the specification; or pharmaceutically-acceptable salt or solvate or stereoisomer thereof. The invention also directed to pharmaceutical compositions containing such compounds; processes and intermediates useful for preparing such compounds; and methods for treating disease conditions mediated by muscarinic receptors using such compounds.

公开(公告)号：US20070134729A1

公开(公告)日：2007-06-14

申请号：US11603287

申请日：2006-11-21

Applicant: Burton Christensen ,  Edmund Moran ,  John Griffin ,  J. Judice ,  YongQi Mu ,  John Pace ,  Mathai Mammen ,  James Aggen

Inventor： Burton Christensen ,  Edmund Moran ,  John Griffin ,  J. Judice ,  YongQi Mu ,  John Pace ,  Mathai Mammen ,  James Aggen

IPC: A61K38/16 ,  A61K31/43 ,  A61K31/545 ,  A61K31/407

CPC classification number: C40B30/04 ,  A61K31/00 ,  A61K47/54 ,  A61K47/55 ,  A61K47/552 ,  A61K47/60 ,  C07C233/36 ,  C07C233/78 ,  C07C237/24 ,  C07C271/20 ,  C07C321/04 ,  C07C323/12 ,  C07C335/08 ,  C07C335/32 ,  C07C2603/18 ,  C07D207/333 ,  C07D211/58 ,  C07D215/56 ,  C07D233/90 ,  C07D235/30 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D413/14 ,  C07D471/04 ,  C07D471/14 ,  C07D473/00 ,  C07D473/34 ,  C07D475/04 ,  C07D475/08 ,  C07D487/04 ,  C07D487/06 ,  C07D493/04 ,  C07D493/06 ,  C07H19/20 ,  C12Q1/26 ,  C12Q1/44 ,  C12Q1/48 ,  C12Q1/533 ,  C40B40/04 ,  G01N33/573 ,  G01N33/6842 ,  G01N33/6845 ,  G01N33/92 ,  G01N2500/00 ,  G01N2500/04 ,  G01N2800/044 ,  Y02A50/401 ,  Y02A50/57 ,  Y10S530/807

Abstract: This invention relates to novel multibinding compounds (agents) that are antibacterial agents. The multibinding compounds of the invention comprise from 2-10 ligands covalently connected by a linker or linkers, wherein each of said ligands in their monovalent (i.e., unlinked) state have the ability to bind to a an enzyme involved in cell wall biosynthesis and metabolism, a precursor used in the synthesis of the bacterial cell wall and/or the bacterial cell surface thereby interfere with the synthesis and/or metabolism of the cell wall. In particular the multibinding compounds of the invention comprise from 2-10 ligands covalently connected by a linker or linkers, wherein each of said ligands has a ligand domain capable of binding to penicillin binding proteins, a transpeptidase enzyme, a substrate of a transpeptidase enzyme, a beta-lactamase enzyme, pencillinase enzyme, cephalosporinase enzyme, a transglycoslase enzyme, or a transglycosylase enzyme substrate; Preferably, the ligands are selected from the beta lactam or glycopeptide class of antibacterial agents.

Abstract translation: 本发明涉及作为抗菌剂的新型多结合化合物（试剂）。 本发明的多相结合化合物包含2-10个配体，其通过连接体或连接体共价连接，其中所述各单体（即，未连接）状态的所述配体具有结合涉及细胞壁生物合成和代谢的酶的能力 用于合成细菌细胞壁和/或细菌细胞表面的前体因而干扰细胞壁的合成和/或代谢。 特别地，本发明的多相结合化合物包含通过接头或接头共价连接的2-10个配体，其中每个所述配体具有能够结合青霉素结合蛋白的配体结构域，转肽酶，转肽酶的底物， β-内酰胺酶，pencillinase酶，头孢菌素酶，转糖基酶或转糖基酶酶底物; 优选地，配体选自β-内酰胺或糖肽类抗菌剂。

公开(公告)号：US07183292B2

公开(公告)日：2007-02-27

申请号：US10865527

申请日：2004-06-10

Applicant: Mathai Mammen ,  Adam Hughes ,  Yu-hua Ji ,  Li Li ,  Weijiang Zhang

Inventor： Mathai Mammen ,  Adam Hughes ,  Yu-hua Ji ,  Li Li ,  Weijiang Zhang

IPC: A61K31/445 ,  A61K31/40 ,  C07D207/04 ,  C07D211/06

CPC classification number: C07D207/08 ,  A61K31/40 ,  C07D207/09 ,  C07D207/16 ,  C07D211/34

Abstract: This invention is directed to compounds of formula I: wherein R1–R5 and a-e are as defined in the specification; or pharmaceutically-acceptable salt or solvate or stereoisomer thereof. The invention also directed to pharmaceutical compositions containing such compounds; processes and intermediates useful for preparing such compounds; and methods for treating disease conditions mediated by muscarinic receptors using such compounds.

Abstract translation: 本发明涉及式I化合物：其中R 1 -R 5和a-e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。 本发明还涉及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。