公开(公告)号：US20090111737A1

公开(公告)日：2009-04-30

申请号：US12082666

申请日：2008-04-11

申请人： Burton G. Christensen ,  Edmund J. Moran ,  John H. Griffin ,  J. Kevin Judice ,  YongQi Mu ,  John L. Pace ,  Mathai Mammen ,  James Aggen

发明人： Burton G. Christensen ,  Edmund J. Moran ,  John H. Griffin ,  J. Kevin Judice ,  YongQi Mu ,  John L. Pace ,  Mathai Mammen ,  James Aggen

IPC分类号： A61K38/14 ,  C07K7/00 ,  A61P43/00

CPC分类号： C07D477/12 ,  C07D499/32 ,  C07D499/44 ,  C07D501/56

摘要： 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.

摘要翻译： 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：US07456203B2

公开(公告)日：2008-11-25

申请号：US10425368

申请日：2003-04-29

申请人： James Aggen ,  John H. Griffin ,  Mathai Mammen ,  Daniel Marquess ,  Edmund J. Moran ,  David Oare

发明人： James Aggen ,  John H. Griffin ,  Mathai Mammen ,  Daniel Marquess ,  Edmund J. Moran ,  David Oare

IPC分类号： A01N43/40 ,  A61K31/445

CPC分类号： A61K31/40 ,  C07C211/32 ,  C07C2603/32 ,  C07D207/08 ,  C07D209/48 ,  C07D211/46 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D519/00 ,  G01N33/566

摘要： Disclosed are multibinding compounds which are muscarinic receptor antagonists. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is, independently of each other, a muscarinic receptor antagonist or an allosteric modulator provided that at least one of said ligand is a muscarinic receptor antagonist. The multibinding compounds of this invention are useful in the treatment and prevention of diseases such as chronic obstructive pulmonary disease, chronic bronchitis, irritable bowel syndrome, urinary incontinence, and the like.

摘要翻译： 公开了作为毒蕈碱受体拮抗剂的多重联结化合物。 含有2-10个配体的本发明的多相结合化合物共价连接到一个或多个接头上。 每个配体彼此独立地是毒蕈碱受体拮抗剂或变构调节剂，只要至少一种所述配体是毒蕈碱受体拮抗剂即可。 本发明的多重联结化合物可用于治疗和预防慢性阻塞性肺疾病，慢性支气管炎，肠易激综合征，尿失禁等疾病。

公开(公告)号：US06693202B1

公开(公告)日：2004-02-17

申请号：US09645609

申请日：2000-08-25

申请人： James Aggen ,  John H. Griffin ,  Mathai Mammen ,  Daniel Marquess ,  Edmund J. Moran ,  David Oare

发明人： James Aggen ,  John H. Griffin ,  Mathai Mammen ,  Daniel Marquess ,  Edmund J. Moran ,  David Oare

IPC分类号： C07D20700

CPC分类号： A61K31/40 ,  C07C211/32 ,  C07C2603/32 ,  C07D207/08 ,  C07D209/48 ,  C07D211/46 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D519/00 ,  G01N33/566

摘要： Disclosed are multibinding compounds which are muscarinic receptor antagonists. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is, independently of each other, a muscarinic receptor antagonist or an allosteric modulator provided that at least one of said ligand is a muscarinic receptor antagonist. The multibinding compounds of this invention are useful in the treatment and prevention of diseases such as chronic obstructive pulmonary disease, chronic bronchitis, irritable bowel syndrome, urinary incontinence, and the like.

摘要翻译： 公开了作为毒蕈碱受体拮抗剂的多重联结化合物。 含有2-10个配体的本发明的多相结合化合物共价连接到一个或多个接头上。 每个配体彼此独立地是毒蕈碱受体拮抗剂或变构调节剂，只要至少一种所述配体是毒蕈碱受体拮抗剂即可。 本发明的多重联结化合物可用于治疗和预防慢性阻塞性肺疾病，慢性支气管炎，肠易激综合征，尿失禁等疾病。

公开(公告)号：US20090306134A1

公开(公告)日：2009-12-10

申请号：US12286528

申请日：2008-09-30

申请人： James Aggen ,  John H. Griffin ,  Mathai Mammen ,  Daniel Marquess ,  Edmund J. Moran ,  David Oare

发明人： James Aggen ,  John H. Griffin ,  Mathai Mammen ,  Daniel Marquess ,  Edmund J. Moran ,  David Oare

IPC分类号： A61K31/4545 ,  A61K31/54 ,  A61K31/5377 ,  A61K31/495 ,  A61K31/445 ,  C07D413/12 ,  C07D403/06 ,  C07D401/06 ,  C07D211/00

CPC分类号： A61K31/40 ,  C07C211/32 ,  C07C2603/32 ,  C07D207/08 ,  C07D209/48 ,  C07D211/46 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D519/00 ,  G01N33/566

摘要： Disclosed are multibinding compounds which are muscarinic receptor antagonists. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is, independently of each other, a muscarinic receptor antagonist or an allosteric modulator provided that at least one of said ligand is a muscarinic receptor antagonist. The multibinding compounds of this invention are useful in the treatment and prevention of diseases such as chronic obstructive pulmonary disease, chronic bronchitis, irritable bowel syndrome, urinary incontinence, and the like.

摘要翻译： 公开了作为毒蕈碱受体拮抗剂的多重联结化合物。 含有2-10个配体的本发明的多相结合化合物共价连接到一个或多个接头上。 每个配体彼此独立地是毒蕈碱受体拮抗剂或变构调节剂，只要至少一种所述配体是毒蕈碱受体拮抗剂即可。 本发明的多重联结化合物可用于治疗和预防慢性阻塞性肺疾病，慢性支气管炎，肠易激综合征，尿失禁等疾病。

公开(公告)号：US20070196859A1

公开(公告)日：2007-08-23

申请号：US11603329

申请日：2006-11-21

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

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

IPC分类号： A61K38/14 ,  A61K31/43 ,  A61K31/545 ,  A61K31/407

CPC分类号： C07D477/12 ,  C07D499/32 ,  C07D499/44 ,  C07D501/56

摘要： 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, penicillinase enzyme, cephalosporinase enzyme, a transglycosylase enzyme, or a transglycosylase enzyme substrate; Preferably, the ligands are selected from the beta lactam or glycopeptide class of antibacterial agents.

摘要翻译： 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，青霉素酶，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：US20070154948A1

公开(公告)日：2007-07-05

申请号：US11603286

申请日：2006-11-21

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

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

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

CPC分类号： C07D477/12 ,  C07D499/32 ,  C07D499/44 ,  C07D501/56

摘要： 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：US20070134729A1

公开(公告)日：2007-06-14

申请号：US11603287

申请日：2006-11-21

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

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

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

CPC分类号： 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

摘要： 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.

摘要翻译： 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：US20160220551A1

公开(公告)日：2016-08-04

申请号：US15016528

申请日：2016-02-05

申请人： Mathai Mammen ,  YuHua Ji ,  YongQi Mu ,  Craig Husfeld ,  Li Li

发明人： Mathai Mammen ,  YuHua Ji ,  YongQi Mu ,  Craig Husfeld ,  Li Li

IPC分类号： A61K31/4545 ,  A61K45/06 ,  A61K9/16

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

摘要： 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：US08377966B2

公开(公告)日：2013-02-19

申请号：US13357891

申请日：2012-01-25

申请人： YongQi Mu ,  YuHua Ji ,  Mathai Mammen ,  Viengkham Malathong

发明人： YongQi Mu ,  YuHua Ji ,  Mathai Mammen ,  Viengkham Malathong

IPC分类号： A61K31/4523 ,  C07D211/40 ,  C07D401/12

CPC分类号： C07D211/46 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12

摘要： The invention provides compounds of formula I: wherein a, b, c, m, n, q, r, W, Z1, Ar1, Z2, Y, R1, R2, and R3 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：US08329911B2

公开(公告)日：2012-12-11

申请号：US12616957

申请日：2009-11-12

申请人： YongQi Mu ,  YuHua Ji ,  Mathai Mammen ,  Eric L. Stangeland

发明人： YongQi Mu ,  YuHua Ji ,  Mathai Mammen ,  Eric L. Stangeland

IPC分类号： C07D211/46 ,  A61K31/445

CPC分类号： C07D211/46 ,  C07D405/12

摘要： The invention provides compounds of formula I: wherein a, b, c, p, W, A, X1, R1, R2, R3, 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.

摘要翻译： 本发明提供式I化合物：其中a，b，c，p，W，A，X 1，R 1，R 2，R 3，R 6，R 7和R 8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。