公开(公告)号：US09296759B2

公开(公告)日：2016-03-29

申请号：US14346252

申请日：2012-09-21

Applicant: AMGEN INC.

Inventor： Ryan White ,  Yuan Cheng ,  Ana Elena Minatti ,  Bryant Yang ,  Xiao Mei Zheng ,  Patricia Lopez ,  Jason B. Human ,  Oleg Epstein ,  Ted Judd ,  Kelvin Sham ,  Qiufen Xue

IPC: C07D498/20 ,  C07D513/20 ,  A61K31/537 ,  A61K31/547 ,  C07D513/10 ,  C07D498/10

CPC classification number: C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C07D513/20

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 A1, A2, A3, A4, A5, A6, L, 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.

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中的A1，A2，A3，A4，A5，A6，L，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：US20150031668A1

公开(公告)日：2015-01-29

申请号：US14331426

申请日：2014-07-15

Applicant: AMGEN INC.

Inventor： Kaustav Biswas ,  Jian J. Chen ,  Vijay Keshav Gore ,  Scott Harried ,  Daniel B. Horne ,  Matthew R. Kaller ,  Vu Van Ma ,  Kelvin Sham ,  James Brown ,  Wenge Zhong ,  Thomas T. Nguyen

IPC: C07D491/052 ,  C07D498/04 ,  C07D471/04

CPC classification number: C07D491/052 ,  C07D471/04 ,  C07D498/04

Abstract: Chroman compounds and derivatives of Formula I are useful inhibitors of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

Abstract translation: 色甘酸化合物和式I的衍生物是TRPM8的有用抑制剂。 这些化合物可用于治疗多种TRPM8介导的病症和病症，并且可用于制备用于治疗这种病症和病症的药物和药物组合物。 这些疾病的实例包括但不限于偏头痛和神经性疼痛。 式I的化合物具有以下结构：其中本文提供变量的定义。