公开(公告)号：US09346798B2

公开(公告)日：2016-05-24

申请号：US14377478

申请日：2013-02-12

申请人： AMGEN INC.

发明人： Christiane Boezio ,  Alessandro Boezio ,  Howard Bregman ,  Nagasree Chakka ,  James R. Coats ,  Katrina Woodin Copeland ,  Erin F. Dimauro ,  Thomas Dineen ,  Hua Gao ,  Daniel La ,  Isaac E. Marx ,  Hanh Nho Nguyen ,  Emily Anne Peterson ,  Matthew Weiss

IPC分类号： C07D413/12 ,  C07D417/12 ,  C07D413/14 ,  C07D471/04 ,  C07D417/14

CPC分类号： C07D417/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

摘要： The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

摘要翻译： 本发明提供式I化合物或其药学上可接受的盐，其是电压门控钠通道的抑制剂，特别是Nav 1.7。 该化合物可用于治疗可通过抑制钠通道（例如疼痛障碍）治疗的疾病。 还提供含有本发明化合物的药物组合物。

公开(公告)号：US09212182B2

公开(公告)日：2015-12-15

申请号：US14302337

申请日：2014-06-11

申请人： AMGEN INC.

发明人： Matthew Weiss ,  Alessandro Boezio ,  Christiane Boezio ,  John R. Butler ,  Margaret Yuhua Chu-Moyer ,  Erin F. Dimauro ,  Thomas Dineen ,  Russell Graceffa ,  Angel Guzman-Perez ,  Hongbing Huang ,  Charles Kreiman ,  Daniel La ,  Isaac E. Marx ,  Benjamin Charles Milgrim ,  Hanh Nho Nguyen ,  Emily Peterson ,  Karina Romero ,  Brian Sparling

IPC分类号： A61K31/00 ,  C07D215/00 ,  C07D471/04 ,  C07D413/12 ,  C07D401/12 ,  C07D413/14 ,  C07D417/12 ,  C07C53/18 ,  C07D215/227 ,  C07D403/12 ,  C07D215/36 ,  C07D241/44

CPC分类号： C07D417/14 ,  C07C53/18 ,  C07D215/227 ,  C07D215/36 ,  C07D241/44 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

摘要： The present invention provides compounds of Formula I, and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

摘要翻译： 本发明提供式I化合物及其药学上可接受的盐，其是电压门控钠通道的抑制剂，特别是Nav1.7。 该化合物可用于治疗与钠通道活性相关的疾病，例如疼痛障碍和瘙痒。 还提供含有本发明化合物的药物组合物。

公开(公告)号：US09012443B2

公开(公告)日：2015-04-21

申请号：US13707096

申请日：2012-12-06

申请人： Amgen Inc.

发明人： Christiane Boezio ,  Howard Bregman ,  James R. Coats ,  Erin F. Dimauro ,  Thomas Dineen ,  Bingfan Du ,  Russell Graceffa ,  Charles Kreiman ,  Daniel La ,  Isaac E. Marx ,  Nagasree Chakka ,  Hanh Nho Nguyen ,  Emily Anne Peterson ,  Matthew Weiss ,  Katrina W. Copeland ,  Holly L. Deak ,  Alessandro Boezio

IPC分类号： C07D498/04 ,  C07D417/12 ,  C07D417/14 ,  C07D401/14 ,  C07D471/04 ,  A61K31/433 ,  C07D403/12 ,  C07D413/14 ,  C07D401/12 ,  C07D403/14 ,  C07D239/42 ,  C07D409/14 ,  C07D413/12 ,  C07D277/52 ,  C07D285/08

CPC分类号： C07D498/04 ,  C07D239/42 ,  C07D277/52 ,  C07D285/08 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

摘要： The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

摘要翻译： 本发明提供式I化合物或其药学上可接受的盐，其是电压门控钠通道的抑制剂，特别是Nav 1.7。 该化合物可用于治疗可通过抑制钠通道（例如疼痛障碍）治疗的疾病。 还提供含有本发明化合物的药物组合物。

公开(公告)号：US10729684B2

公开(公告)日：2020-08-04

申请号：US16062602

申请日：2016-12-19

申请人： AMGEN INC.

发明人： Matthew Weiss ,  Thomas Dineen ,  Karina R. Vaida

IPC分类号： C07D215/36 ,  A61K31/4704 ,  C07D241/44 ,  C07D403/12 ,  C07D413/14 ,  C07D417/12 ,  C07D413/12 ,  A61P29/02 ,  A61P11/14 ,  A61K31/501

摘要： The present invention provides compounds of Formula I, and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

公开(公告)号：US09458152B2

公开(公告)日：2016-10-04

申请号：US14920833

申请日：2015-10-22

申请人： AMGEN INC.

发明人： Matthew Weiss ,  Alessandro Boezio ,  Christiane Boezio ,  John R. Butler ,  Margaret Yuhua Chu-Moyer ,  Erin F. Dimauro ,  Thomas Dineen ,  Russell Graceffa ,  Angel Guzman-Perez ,  Hongbing Huang ,  Charles Kreiman ,  Daniel La ,  Isaac E. Marx ,  Benjamin Charles Milgram ,  Hanh Nho Nguyen ,  Emily Anne Peterson ,  Karina R. Vaida ,  Brian Sparling

IPC分类号： A61K31/00 ,  C07D417/14 ,  C07D471/04 ,  C07D413/12 ,  C07D401/12 ,  C07D413/14 ,  C07D417/12 ,  C07C53/18 ,  C07D215/227 ,  C07D403/12 ,  C07D215/36 ,  C07D241/44 ,  C07D401/14

CPC分类号： C07D417/14 ,  C07C53/18 ,  C07D215/227 ,  C07D215/36 ,  C07D241/44 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

摘要： The present invention provides compounds of Formula I, and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

公开(公告)号：US20150057271A1

公开(公告)日：2015-02-26

申请号：US14377478

申请日：2013-02-12

申请人： AMGEN INC.

发明人： Christiane Boezio ,  Alessandro Boezio ,  Howard Bregman ,  Nagasree Chakka ,  James R. Coats ,  Katrina Woodin Copeland ,  Erin F. Dimauro ,  Thomas Dineen ,  Hua Gao ,  Daniel La ,  Isaac E. Marx ,  Hanh Nho Nguyen ,  Emily Anne Peterson ,  Matthew Weiss

IPC分类号： C07D417/14 ,  C07D471/04 ,  C07D413/14 ,  C07D417/12 ,  C07D413/12

CPC分类号： C07D417/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

摘要： The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

摘要翻译： 本发明提供式I化合物或其药学上可接受的盐，其是电压门控钠通道的抑制剂，特别是Nav 1.7。 该化合物可用于治疗可通过抑制钠通道（例如疼痛障碍）治疗的疾病。 还提供含有本发明化合物的药物组合物。

公开(公告)号：US09776995B2

公开(公告)日：2017-10-03

申请号：US14898070

申请日：2014-06-11

申请人： AMGEN INC.

发明人： Matthew Weiss ,  Erin F. DiMauro ,  Thomas Dineen ,  Russell Graceffa ,  Angel Guzman-Perez ,  Hongbing Huang ,  Charles Kreiman ,  Isaac E. Marx ,  Hanh Nho Nguyen ,  Emily Anne Peterson ,  Holly L. Deak

IPC分类号： C07D417/14 ,  C07D471/04 ,  C07D413/12 ,  C07D401/12 ,  C07D413/14 ,  C07D417/12 ,  C07C53/18 ,  C07D215/227 ,  C07D403/12 ,  C07D215/36 ,  C07D241/44 ,  C07D401/14

CPC分类号： C07D417/14 ,  C07C53/18 ,  C07D215/227 ,  C07D215/36 ,  C07D241/44 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

摘要： The present invention provides compounds of Formula I or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

公开(公告)号：US09012446B2

公开(公告)日：2015-04-21

申请号：US13929483

申请日：2013-06-27

申请人： Amgen Inc.

发明人： Jian Chen ,  Wenge Zhong ,  Patricia Lopez ,  Ryan White ,  Matthew Weiss ,  Ted Judd ,  Timothy Powers ,  Yuan Cheng ,  Thomas Dineen ,  Jonathan D. Low ,  Isaac E. Marx ,  Ana Elena Minatti

IPC分类号： C07D498/10 ,  C07D498/20 ,  C07D513/20 ,  C07D513/10

CPC分类号： C07D513/10 ,  C07D498/10 ,  C07D498/20 ,  C07D513/20

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

摘要翻译： 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中式I中的A1，A2，A3，A4，A5，A6，R2，R7，X，Y和Z如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。 这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

公开(公告)号：US10472356B2

公开(公告)日：2019-11-12

申请号：US15554801

申请日：2016-03-02

申请人： AMGEN INC.

发明人： Matthew Weiss ,  Benjamin Charles Milgram ,  Thomas Dineen ,  John Stellwagen ,  Angel Guzman-Perez ,  Alessandro Boezio ,  Issac E. Marx

IPC分类号： A61K31/4375 ,  C07D471/04

摘要： The present invention provides compounds of Formula (I), wherein: as defined in the specification, an enantiomer, diastereomer, atropisomer thereof, or a mixture thereof, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders, cough, or itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

公开(公告)号：US10383866B2

公开(公告)日：2019-08-20

申请号：US16062606

申请日：2016-12-19

申请人： AMGEN INC.

发明人： Matthew Weiss ,  Thomas Dineen ,  Benjamin C. Milgram

IPC分类号： C07D403/12 ,  C07D413/12 ,  A61K31/4704 ,  A61K31/501 ,  A61P11/14 ,  A61P29/02

摘要： The present invention provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.