公开(公告)号：WO2016022724A1

公开(公告)日：2016-02-11

申请号：PCT/US2015/043868

申请日：2015-08-05

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer R. ,  AMEGADZIE, Albert ,  BOURBEAU, Matthew P. ,  BROWN, James A. ,  CHEN, Jian J. ,  CHENG, Yuan ,  FROHN, Michael J. ,  GUZMAN-PEREZ, Angel ,  HARRINGTON, Paul E. ,  LIU, Longbin ,  LIU, Qingyian ,  LOW, Jonathan D. ,  MA, Vu Van ,  MANNING, James ,  MINATTI, Ana Elena ,  NGUYEN, Thomas T. ,  NISHMURA, Nobuko ,  NORMAN, Mark H. ,  PETTUS, Liping H. ,  PICKRELL, Alexander J. ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  SIEGMUND, Aaron C. ,  STEC, Markian M. ,  WHITE, Ryan ,  XUE, Qiufen

IPC: C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  A61K31/5415 ,  A61P25/28 ,  C07D279/08

CPC classification number: C07D417/12 ,  C07D279/08 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D513/10

Abstract: 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 A 4 , A 5 , A 6 , A 8 , and each of R a , R b , R 1 , R 2 , R 3 and R 7 of Formula (I), independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and 15 deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas (II) and (III), and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

Abstract translation: 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）的各个变量A4，A5，A6，A8和R a，R b，R 1，R 2，R 3和R 7各自独立地在本文中定义。 本发明还提供了包含该化合物的药物组合物，以及该化合物和组合物用于治疗由BACE生物活性导致的A-β斑块形成和15沉积相关的病症和/或病症的用途。 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）和（III）的化合物及其分子式实施方案，用于制备本发明化合物的中间体和方法。