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    • 6. 发明申请
    • SPIRO-AMINO-IMIDAZO-FUSED HETEROCYCLIC COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
    • 作为β-分泌酶调节剂的螺旋 - 氨基 - 咪唑 - 稠合的杂环化合物及其使用方法
    • WO2012112462A1
    • 2012-08-23
    • PCT/US2012/024918
    • 2012-02-13
    • AMGEN INC.EPSTEIN, OlegWHITE, RyanPATEL, Vinod F.HUMAN, Jason
    • EPSTEIN, OlegWHITE, RyanPATEL, Vinod F.HUMAN, Jason
    • C07D491/00A61K31/353A61P25/00
    • C07D491/20A61K31/353
    • 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 1 , A 3 , A 4 , A 5 , A 6 , A 8 , R 2 , R 7 , X, Y and Z of Formula I 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 plaque formation and deposition, resulting from the activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits and impairments, schizophrenia and other central nervous system conditions and disorders. The invention further provides compounds of Formulas II and III, and of sub-formulas of Formulas I, II and III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.
    • 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A1,A3,A4,A5,A6,A8,R2,R7,X,Y和Z如本文所定义。 本发明还提供包含该化合物的药物组合物,以及用于治疗由于BACE的活性而导致的与斑块形成和沉积有关的疾病和/或病症的化合物和组合物的相应用途。 这种BACE介导的病症包括例如阿尔茨海默病,认知缺陷和损伤,精神分裂症和其他中枢神经系统病症和障碍。 本发明还提供了式II和III的化合物和式I,II和III的分子式,可用于制备式I-III化合物的中间体和方法和方法。