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    • 1. 发明申请
    • CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE
    • 色氨酸,异色烯和二氢异苯并呋喃衍生物作为mGluR2-阴离子调节剂,组合物和它们的用途
    • WO2018063955A1
    • 2018-04-05
    • PCT/US2017/053155
    • 2017-09-25
    • MERCK SHARP & DOHME CORP.SEBHAT, Iyassu, K.ARASAPPAN, AshokHOYT, Scott, B.WILKENING, Robert, R.DEMONG, Duane
    • SEBHAT, Iyassu, K.ARASAPPAN, AshokHOYT, Scott, B.WILKENING, Robert, R.DEMONG, Duane
    • C07D491/04C07D491/18A61K31/436A61P25/00
    • The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from (II), (III), (IV), and (V), and ring B, n, R 1 , R 2 , R 2A , R 3 , and R 3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild congnitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.
    • 本发明提供了式(I)的某些取代的苯并二氢吡喃,异苯并二氢吡喃和二氢异苯并呋喃化合物或其药学上可接受的盐,其中环A是选自(II),(III),( IV)和(V)中,并且环B,n,R 1,R 2,R 2A,R 3, 和R 3A如本文所定义。 本发明化合物可用作mGluR2抑制剂或mGluR2阴变构调节剂(NAM),并且可用于治疗患者涉及其中涉及mGluR2-NAM受体的疾病或病症如阿尔茨海默病,认知 通过给患者施用治疗有效量的本发明化合物或其药学上可接受的盐,减轻,轻度认知障碍,精神分裂症和其他情绪障碍,疼痛障碍和睡眠障碍。 本发明还涉及包含本发明化合物或其药学上可接受的盐(任选与一种或多种另外的活性成分组合)和药学上可接受的载体的药物组合物,以及所述化合物和药物组合物 本发明在治疗这些疾病中的应用。