公开(公告)号：US08217052B2

公开(公告)日：2012-07-10

申请号：US13151925

申请日：2011-06-02

申请人： Zhongli Gao ,  Ryan Hartung ,  David Stefany

发明人： Zhongli Gao ,  Ryan Hartung ,  David Stefany

IPC分类号： A61K31/438 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/407 ,  C07D491/107 ,  C07D401/04 ,  C07D401/14 ,  C07D401/02

CPC分类号： C07D491/107

摘要： The present disclosure relates to a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I): wherein R1, R2, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefore are disclosed.

摘要翻译： 本公开涉及一系列式（I）的取代的N-苯基 - 联吡咯烷甲酰胺：其中R 1，R 2，m，n和p如本文所述。 更具体地，本发明的化合物是H3受体的调节剂，因此可用作药剂，特别是用于治疗和/或预防由H3受体调节的各种疾病，包括与中枢神经系统相关的疾病。 另外，公开了制备取代的N-苯基 - 联吡咯烷甲酰胺和中间体的方法。

公开(公告)号：US20090036469A1

公开(公告)日：2009-02-05

申请号：US12246918

申请日：2008-10-07

申请人： David STEFANY ,  Keith John HARRIS ,  Timothy Alan GILLESPY ,  Charles J. GARDNER ,  Joacy C. AGUIAR

发明人： David STEFANY ,  Keith John HARRIS ,  Timothy Alan GILLESPY ,  Charles J. GARDNER ,  Joacy C. AGUIAR

IPC分类号： C07D239/47 ,  A61K31/506 ,  A61K31/505 ,  C07D401/04 ,  C07D409/04 ,  A61K31/495 ,  A61P37/08 ,  A61P17/00 ,  A61P11/00

CPC分类号： C07D403/04 ,  C07D239/47 ,  C07D409/04

摘要： The present invention is directed to a compound of formula (I), wherein R1 and R2 are as defined herein, a pharmaceutical composition comprising a pharmaceutically effective amount of one or more compounds of the invention in admixture with a pharmaceutically acceptable carrier, and a method of treating a patient suffering from a PGD2-mediated disorder by administering to said patient a pharmaceutically effective amount of a compound of the invention.

摘要翻译： 本发明涉及式（I）化合物，其中R 1和R 2如本文所定义，药物组合物包含药学上有效量的一种或多种本发明化合物与药学上可接受的载体的混合物，以及方法 通过向所述患者施用药学有效量的本发明化合物来治疗患有PGD2介导的病症的患者。

公开(公告)号：US20070032489A1

公开(公告)日：2007-02-08

申请号：US11535127

申请日：2006-09-26

申请人： Philip Weintraub ,  Paul Eastwood ,  Shujaath Mehdi ,  David Stefany ,  Kwon Musick ,  Neil Moorcroft ,  Sungtaek Lim ,  John Jiang ,  Hartmut Rutten ,  Stefan Peukert ,  Uwe Schwahn

发明人： Philip Weintraub ,  Paul Eastwood ,  Shujaath Mehdi ,  David Stefany ,  Kwon Musick ,  Neil Moorcroft ,  Sungtaek Lim ,  John Jiang ,  Hartmut Rutten ,  Stefan Peukert ,  Uwe Schwahn

IPC分类号： A61K31/5377 ,  A61K31/44 ,  C07D413/02 ,  C07D211/72

CPC分类号： C07D213/64 ,  C07D217/24 ,  C07D401/04 ,  C07D401/14 ,  C07D405/04 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/14

摘要： The present invention relates to a series of 2,3,5-substituted pyridone derivatives of formula I: wherein R, R1, R2, R3 and R4 are as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5′-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.

摘要翻译： 本发明涉及一系列式I的2,3,5-取代吡啶酮衍生物：其中R 1，R 2，R 2，R 3， R 3和R 4如本文所定义。 本发明还涉及制备这些化合物的方法。 本发明的化合物是聚（腺苷5'-二磷酸核糖）聚合酶（PARP）的抑制剂，因此可用作药剂，特别是用于治疗和/或预防各种疾病，包括与中枢神经相关的疾病 系统和心血管疾病。

公开(公告)号：US20120238757A1

公开(公告)日：2012-09-20

申请号：US13483503

申请日：2012-05-30

申请人： Zhongli GAO ,  Ryan HARTUNG ,  David STEFANY

发明人： Zhongli GAO ,  Ryan HARTUNG ,  David STEFANY

IPC分类号： C07D491/107

CPC分类号： C07D491/107

摘要： The present disclosure relates to a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I): wherein R1, R2, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefore are disclosed.

摘要翻译： 本公开涉及一系列式（I）的取代的N-苯基 - 联吡咯烷甲酰胺：其中R 1，R 2，m，n和p如本文所述。 更具体地，本发明的化合物是H3受体的调节剂，因此可用作药剂，特别是用于治疗和/或预防由H3受体调节的各种疾病，包括与中枢神经系统相关的疾病。 另外，公开了制备取代的N-苯基 - 联吡咯烷甲酰胺和中间体的方法。

公开(公告)号：US08193183B2

公开(公告)日：2012-06-05

申请号：US11735751

申请日：2007-04-16

申请人： Sungtaek Lim ,  Keith John Harris ,  David Stefany ,  Charles J. Gardner ,  Bin Cao ,  Ray Boffey ,  Timothy A. Gillespy ,  Joacy C. Aguiar ,  Hazel J. Dyke ,  Elsa A. Dechaux

发明人： Sungtaek Lim ,  Keith John Harris ,  David Stefany ,  Charles J. Gardner ,  Bin Cao ,  Ray Boffey ,  Timothy A. Gillespy ,  Joacy C. Aguiar ,  Hazel J. Dyke ,  Elsa A. Dechaux

IPC分类号： C07D239/47 ,  C07D413/12 ,  A61K31/505 ,  A61K31/5355 ,  A61P37/00 ,  A61P37/08 ,  A61P17/00

CPC分类号： C07D239/42 ,  C07D239/47 ,  C07D239/48 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14

摘要： The present invention is directed to a compound of Formula (I) wherein Cy1, Cy2, L1, L2, and R1 are as defined herein, a pharmaceutical composition comprising a pharmaceutically effective amount of one or more compounds according to Formula (I) in admixture with a pharmaceutically acceptable carrier, and a method of treating a patient suffering from a PGD2-mediated disorder including, but not limited to, allergic disease (such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, disorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, bronchitis, urticaria, eczema, diseases accompanied by itch (such as atopic dermatitis and urticaria), diseases (such as cataract, retinal detachment, inflammation, infection and sleeping disorders) which is generated secondarily as a result of behavior accompanied by itch (such as scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis and the like by administering to said patient a pharmaceutically effective amount of a compound according to Formula (I).

摘要翻译： 本发明涉及式（I）的化合物，其中Cy1，Cy2，L1，L2和R1如本文所定义，药物组合物包含药学上有效量的一种或多种式（I）化合物的混合物 与药学上可接受的载体和治疗患有PGD2介导的病症的患者的方法，包括但不限于过敏性疾病（例如过敏性鼻炎，过敏性结膜炎，特应性皮炎，支气管哮喘和食物过敏），系统性肥大细胞增多症 ，伴有系统性肥大细胞活化，过敏性休克，支气管收缩，支气管炎，荨麻疹，湿疹，伴有瘙痒的疾病（例如特应性皮炎和荨麻疹），疾病（例如白内障，视网膜脱离，炎症，感染和睡眠障碍） 由于伴随瘙痒的行为（如刮伤和跳动），炎症，慢性阻塞性肺疾病 脑缺血再灌注损伤，脑血管意外，慢性类风湿性关节炎，胸膜炎，溃疡性结肠炎等，通过向所述患者施用药学有效量的根据式（I）的化合物。

公开(公告)号：US20110251225A1

公开(公告)日：2011-10-13

申请号：US13151925

申请日：2011-06-02

申请人： Zhongli GAO ,  Ryan HARTUNG ,  David STEFANY

发明人： Zhongli GAO ,  Ryan HARTUNG ,  David STEFANY

IPC分类号： A61K31/438 ,  A61K31/407 ,  A61K31/454 ,  A61K31/4545 ,  A61P25/28 ,  A61P25/14 ,  A61P25/00 ,  A61P25/24 ,  A61P25/18 ,  A61P25/16 ,  A61P25/20 ,  A61P3/04 ,  C07D491/107 ,  A61P25/22

CPC分类号： C07D491/107

摘要： The present disclosure relates to a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I): wherein R1, R2, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefore are disclosed.

摘要翻译： 本公开涉及一系列式（I）的取代的N-苯基 - 联吡咯烷甲酰胺：其中R 1，R 2，m，n和p如本文所述。 更具体地，本发明的化合物是H3受体的调节剂，因此可用作药剂，特别是用于治疗和/或预防由H3受体调节的各种疾病，包括与中枢神经系统相关的疾病。 另外，公开了制备取代的N-苯基 - 联吡咯烷甲酰胺和中间体的方法。

公开(公告)号：US20070244131A1

公开(公告)日：2007-10-18

申请号：US11735751

申请日：2007-04-16

申请人： Sungtaek Lim ,  Keith Harris ,  David Stefany ,  Charles Gardner ,  Bin Cao ,  Ray Boffey ,  Timothy Gillespy ,  Joacy Aguiar ,  Hazel Dyke ,  Elsa Dechaux

发明人： Sungtaek Lim ,  Keith Harris ,  David Stefany ,  Charles Gardner ,  Bin Cao ,  Ray Boffey ,  Timothy Gillespy ,  Joacy Aguiar ,  Hazel Dyke ,  Elsa Dechaux

IPC分类号： A61K31/506 ,  C07D239/47 ,  C07D239/48 ,  C07D239/52

CPC分类号： C07D239/42 ,  C07D239/47 ,  C07D239/48 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14

摘要： The present invention is directed to a compound of Formula (I) wherein Cy1, Cy2, L1, L2, and R1 are as defined herein, a pharmaceutical composition comprising a pharmaceutically effective amount of one or more compounds according to Formula (I) in admixture with a pharmaceutically acceptable carrier, and a method of treating a patient suffering from a PGD2-mediated disorder including, but not limited to, allergic disease (such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, disorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, bronchitis, urticaria, eczema, diseases accompanied by itch (such as atopic dermatitis and urticaria), diseases (such as cataract, retinal detachment, inflammation, infection and sleeping disorders) which is generated secondarily as a result of behavior accompanied by itch (such as scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis and the like by administering to said patient a pharmaceutically effective amount of a compound according to Formula (I).

公开(公告)号：US08383814B2

公开(公告)日：2013-02-26

申请号：US13483503

申请日：2012-05-30

申请人： Zhongli Gao ,  Ryan Hartung ,  David Stefany

发明人： Zhongli Gao ,  Ryan Hartung ,  David Stefany

IPC分类号： C07D491/107 ,  C07D401/04 ,  C07D401/14 ,  C07D401/02

CPC分类号： C07D491/107

摘要： The present disclosure relates to a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I): wherein R1, R2, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefore are disclosed.

摘要翻译： 本公开涉及一系列式（I）的取代的N-苯基 - 联吡咯烷甲酰胺：其中R 1，R 2，m，n和p如本文所述。 更具体地，本发明的化合物是H3受体的调节剂，因此可用作药剂，特别是用于治疗和/或预防由H3受体调节的各种疾病，包括与中枢神经系统相关的疾病。 另外，公开了制备取代的N-苯基 - 联吡咯烷甲酰胺和中间体的方法。

公开(公告)号：US20130005728A1

公开(公告)日：2013-01-03

申请号：US13610027

申请日：2012-09-11

申请人： Keith J. HARRIS ,  Joacy C. AGUIAR ,  Patrick Wai-Kwok SHUM ,  Zhicheng ZHAO ,  Gregory B. POLI ,  Gregory STOKLOSA ,  Yong-Mi CHOI-SLEDESKI ,  Stephan REILING ,  David STEFANY ,  Charles GARDNER

发明人： Keith J. HARRIS ,  Joacy C. AGUIAR ,  Patrick Wai-Kwok SHUM ,  Zhicheng ZHAO ,  Gregory B. POLI ,  Gregory STOKLOSA ,  Yong-Mi CHOI-SLEDESKI ,  Stephan REILING ,  David STEFANY ,  Charles GARDNER

IPC分类号： C07D403/04 ,  A61K31/5377 ,  A61K31/506 ,  C07D401/04 ,  A61P37/08 ,  A61P11/06 ,  A61P11/02 ,  A61P17/00 ,  A61P27/02 ,  A61P27/14 ,  A61P11/00 ,  A61P9/10 ,  A61P3/06 ,  A61P3/10 ,  C07D413/04

CPC分类号： C07D403/04

摘要： The present invention is directed to a substituted pyrimidine compound of formula (I) or an enantiomer thereof, or a prodrug or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising such a compound. The invention also includes a method of treatment of a patient by the administration of a pharmaceutically effective amount of such a compound.

摘要翻译： 本发明涉及式（I）的取代嘧啶化合物或其对映异构体或其前药或药学上可接受的盐，或包含该化合物的药物组合物。 本发明还包括通过施用药学有效量的这种化合物来治疗患者的方法。