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    • 6. 发明公开
    • IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE
    • 作为BACE缓蚀剂,组合物及其使用的亚胺二嗪二氧化物化合物
    • EP2485591A1
    • 2012-08-15
    • EP10822571.5
    • 2010-10-06
    • Merck Sharp & Dohme Corp.
    • SCOTT, Jack, D.STAMFORD, Andrew, W.GILBERT, Eric, J.CUMMING, Jared, N.ISERLOH, UlrichWANG, LingyanLI, Wei
    • A01N43/54A61K31/505
    • C07D417/04C07D285/18C07D417/10
    • In its many embodiments, the present invention provides provides certain iminothiadiazine dioxide compounds, including compounds Formula (a) and include tautomers, solvates, prodrugs, esters, and deuterates thereof, and pharmaceutically acceptable salts of said compounds, tautomers, solvates, prodrugs, esters, and deuterates, wherein each of R
      1 , R
      2 , R
      3 , R
      4 , R
      5 , R
      9 , ring A, ring B, ring C, m, n, p, q, -L
      1 -, -L
      2 -,L
      3 -, and L
      4 - is selected independently and as defined herein. The compounds of the invention have, surprisingly and advantageously, improved solution stability. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed.
    • 在其许多实施方案中,本发明提供了某些亚氨基噻二嗪二氧化物化合物,包括式(a)化合物,包括其互变异构体,溶剂化物,前药,酯和氘化物,以及所述化合物的可药用盐,互变异构体,溶剂化物,前药,酯 ,氘代,其中R 1,R 2,R 3,R 4,R 5,R 9,环A,环B,环C,m,n,p,q,-L 1 - , - L 2 - ,L 3-和L 4-独立地选择并如本文所定义。 本发明的化合物令人惊讶且有利地具有改进的溶液稳定性。 还公开了包含一种或多种此类化合物(单独和与一种或多种其它活性剂组合)的药物组合物,以及它们的制备方法和用于治疗与淀粉样蛋白β(Aβ)蛋白相关的病理学,包括阿尔茨海默氏病。