公开(公告)号：WO2010083246A1

公开(公告)日：2010-07-22

申请号：PCT/US2010/020938

申请日：2010-01-13

Applicant: AMGEN INC. ,  ZENG, Qingping ,  YUAN, Chester Chenguang ,  YAO, Guomin ,  WANG, Xianghong ,  TADESSE, Seifu ,  ST. JEAN, JR., David J. ,  REICHELT, Andreas ,  LIU, Qingyian ,  HONG, Fang-Tsao ,  HAN, Nianhe ,  FOTSCH, Christopher H. ,  DAVIS, Carl D. ,  BOURBEAU, Matthew P. ,  ASHTON, Kate S. ,  ALLEN, John G.

Inventor： ZENG, Qingping ,  YUAN, Chester Chenguang ,  YAO, Guomin ,  WANG, Xianghong ,  TADESSE, Seifu ,  ST. JEAN, JR., David J. ,  REICHELT, Andreas ,  LIU, Qingyian ,  HONG, Fang-Tsao ,  HAN, Nianhe ,  FOTSCH, Christopher H. ,  DAVIS, Carl D. ,  BOURBEAU, Matthew P. ,  ASHTON, Kate S. ,  ALLEN, John G.

IPC: C07D409/04 ,  A61K31/427 ,  A61K31/4709

CPC classification number: C07D417/14 ,  C07D417/04

Abstract: The invention relates to thiazole compounds of Formula (I) and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein. The invention also relates to the therapeutic use of such thiazole compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

Abstract translation: 本发明涉及用于治疗由蛋白激酶B（PKB）介导的疾病的式（I）的噻唑化合物及其组合物，其中变量具有本文提供的定义。 本发明还涉及这种噻唑化合物及其组合物治疗与异常细胞生长，癌症，炎症和代谢紊乱相关的疾病的治疗用途。

公开(公告)号：WO2011063233A1

公开(公告)日：2011-05-26

申请号：PCT/US2010/057428

申请日：2010-11-19

Applicant: AMGEN INC. ,  CHENG, Yuan ,  POWERS, Timothy ,  ASHTON, Kate ,  BROWN, James ,  HARRIED, Scott ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  NIXEY, Thomas ,  PARAS, Nick A, ,  POON, Steve F. ,  ST. JEAN JR., David J. ,  XUE, Qiufen ,  ZHONG, Wenge

Inventor： CHENG, Yuan ,  POWERS, Timothy ,  ASHTON, Kate ,  BROWN, James ,  HARRIED, Scott ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  NIXEY, Thomas ,  PARAS, Nick A, ,  POON, Steve F. ,  ST. JEAN JR., David J. ,  XUE, Qiufen ,  ZHONG, Wenge

IPC: C07D215/38 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D405/12 ,  C07D417/04 ,  A61K31/4709 ,  A61P25/28

CPC classification number: C07D215/38 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D405/12 ,  C07D417/04

Abstract: 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 ring A, B 1 , B 2 , B 3 , L, R 1 , R 4 , R 5 and m 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 (AD), 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.

Abstract translation: 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的环A，B 1，B 2，B 3，L，R 1，R 4，R 5和m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疾病和病症的用途。 这些疾病包括例如阿尔茨海默氏病（AD），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。