公开(公告)号：US09663508B2

公开(公告)日：2017-05-30

申请号：US15026740

申请日：2014-10-01

申请人： AMGEN INC.

发明人： Howard Bregman ,  Nagasree Chakka ,  Erin F. Dimauro ,  Hua Gao ,  Hakan Gunaydin ,  Hongbing Huang ,  Philip R. Olivieri ,  Laurie Schenkel ,  Matthew Weiss

IPC分类号： C07D417/12 ,  C07D213/64 ,  C07D213/26 ,  C07D213/643 ,  C07D213/70 ,  C07D401/04 ,  C07D405/12

CPC分类号： C07D417/12 ,  C07D213/26 ,  C07D213/64 ,  C07D213/643 ,  C07D213/70 ,  C07D401/04 ,  C07D405/12

摘要： The present invention provides compounds of Formula (Ia), and pharmaceutically acceptable salts thereof. The compounds are useful as inhibitors of voltage-gated sodium channels, in particular Nav 1.7. as described in the specification. 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, as well as intermediates and processes useful for making the compounds.

公开(公告)号：US20140066430A1

公开(公告)日：2014-03-06

申请号：US14045715

申请日：2013-10-03

申请人： Amgen Inc.

发明人： Victor J. CEE ,  Holly L. DEAK ,  Bingfan DU ,  Stephanie D. GEUNS-MEYER ,  Brian L. HODOUS ,  Hanh Nho NGUYEN ,  Philip R. Olivieri ,  Vinod F. Patel ,  Karina ROMERO ,  Laurie Schenkel

IPC分类号： C07D401/14 ,  C07D491/048 ,  C07D417/14 ,  C07D409/14 ,  C07D471/04 ,  C07D495/04

CPC分类号： C07D401/14 ,  C07D237/30 ,  C07D239/42 ,  C07D401/04 ,  C07D409/04 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048 ,  C07D495/04 ,  C07D497/04

摘要： The present invention relates to chemical compounds having a general formula I wherein A1, A2, C1, C2, D, L1, L2, Z and R3, R4, R6, R7 and R8 are defined herein, which are capable of modulating Aurora kinase protein activity, thereby influencing various disease states and conditions related to the activities of Aurora kinase proteins. For example, the compounds are capable of influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, processes of preparing compounds of the invention, synthetic intermediates and methods of treatment of conditions related to the activity of Aurora kinase.

摘要翻译： 本发明涉及具有通式I的化合物，其中A1，A2，C1，C2，D，L1，L2，Z和R3，R4，R6，R7和R8如本文所定义，其能够调节极光激酶蛋白 活动，从而影响与Aurora激酶蛋白活性相关的各种疾病状态和病症。 例如，化合物能够影响细胞周期和细胞增殖的过程，以治疗癌症和与癌症有关的疾病。 本发明还包括药物组合物，制备本发明化合物的方法，合成中间体和治疗与Aurora激酶活性有关的病症的方法。

公开(公告)号：US09309263B2

公开(公告)日：2016-04-12

申请号：US14166012

申请日：2014-01-28

申请人： AMGEN INC.

发明人： Ryan White ,  Jennifer R. Allen ,  Oleg Epstein ,  Fang-Tsao Hong ,  Zihao Hua ,  Jason Brooks Human ,  Patricia Lopez ,  Philip R. Olivieri ,  Karina Romero ,  Laurie Schenkel ,  John Stellwagen ,  Nuria A. Tamayo ,  Xiao Mei Zheng

IPC分类号： C07D417/10 ,  C07D417/14 ,  C07D513/04 ,  C07D513/14 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/10 ,  C07D513/20 ,  C07D519/00

CPC分类号： C07D513/04 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/10 ,  C07D513/14 ,  C07D513/20 ,  C07D519/00

摘要： The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A5, A6, A8, R1, R2, R3, R7, X, Y, n and o of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, compounds of Formula III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III, and sub-Formulas thereof.

摘要翻译： 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 化合物具有通式I：其中式I的变量A5，A6，A8，R1，R2，R3，R7，X，Y，n和o独立地在本文中定义。 本发明还提供包含该化合物的药物组合物，以及用于治疗由BACE的生物学活性产生的A-β斑块形成和沉积相关的病症和/或病症的化合物和组合物的相应用途。 这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。 本发明还提供式II化合物及其次级实施方案，式III化合物，可用于制备式I-III化合物的中间体和方法和方法及其分式。

公开(公告)号：US09096615B2

公开(公告)日：2015-08-04

申请号：US14445498

申请日：2014-07-29

申请人： AMGEN INC.

发明人： Richard T. Lewis ,  Jennifer R. Allen ,  James Brown ,  Angel Guzman-Perez ,  Zihao Hua ,  Ted Judd ,  Qingyian Liu ,  Philip R. Olivieri ,  Karina Romero ,  Laurie Schenkel ,  John Stellwagen ,  Ryan White

IPC分类号： C07D513/06 ,  C07D513/08 ,  C07D519/00

CPC分类号： C07D513/08 ,  C07D513/06 ,  C07D519/00

摘要： The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A8, R1, R2, R3, R7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, compounds of Formula III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III, and sub-Formulas thereof.

摘要翻译： 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 化合物具有通式I：其中式I的变量A4，A5，A6，A8，R1，R2，R3，R7和n独立地在本文中定义。 本发明还提供包含该化合物的药物组合物，以及用于治疗由BACE的生物学活性产生的A-β斑块形成和沉积相关的病症和/或病症的化合物和组合物的相应用途。 这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。 本发明还提供式II化合物及其次级实施方案，式III化合物，可用于制备式I-III化合物的中间体和方法和方法及其分式。