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    • 79. 发明申请
    • PPAR-(GAMMA) AGONISTS AS AGENTS FOR THE TREATMENT OF TYPE II DIABETES
    • 作为治疗II型糖尿病的药物的PPAR-(GAMMA)激动剂
    • WO00063161A1
    • 2000-10-26
    • PCT/US2000/010416
    • 2000-04-18
    • A61P3/10A61K31/198A61P3/00A61P43/00C07C237/30C07C237/32C07C237/38C07C323/40C07C323/42A61K31/195C07B61/00C07C323/30
    • C07C237/38C07C237/30C07C237/32C07C323/40C07C2601/08C07C2601/14
    • Disclosed are compounds of formula (I) or the pharmaceutically acceptable non-toxic salts thereof wherein: Z is aryl or heteroaryl; n and m are 0, 1 or 2; A is a carboxylic acid or ester; or A is formula (II) where D, F and G are hydrogen, (un)substituted amino, (un)substituted alkoxy, methylene or an (un)substituted sulfide; X is N, O, CH2, S, SO or SO2; R4 is oxo, hydrogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyl, keto, acyl, or sulfonyl; Y is hydrogen, (un)substituted amino, (un)substituted alkoxy, methylene, an (un)substituted sulfide, (un)substituted sulfonyl or an (un)substituted sulfoxide; and R5, R6 and R8 are hydrogen, lower alkyl, lower alkoxy, cycloalkyl, keto, acyl, or sulfonyl; or R5 and R6 together form a ring. The compounds are highly selective agonists for the PPAR- gamma receptor or prodrugs of agonists for the PPAR- gamma receptor. Thus these compounds are useful in the treatment Type II diabetes (NIDDM).
    • 公开了式(I)化合物或其药学上可接受的无毒盐,其中:Z是芳基或杂芳基; n和m为0,1或2; A是羧酸或酯; 或A是式(II)其中D,F和G是氢,(取代的)取代的氨基,(未)取代的烷氧基,亚甲基或(取代的)取代的硫化物; X是N,O,CH2,S,SO或SO2; R4是氧代,氢,羟基,低级烷基,低级烷氧基,环烷基,酮基,酰基或磺酰基; Y是氢,(未)取代的氨基,(未)取代的烷氧基,亚甲基,(未)取代的硫化物,(未)取代的磺酰基或(取代的)亚砜; R5,R6和R8是氢,低级烷基,低级烷氧基,环烷基,酮基,酰基或磺酰基; 或R5和R6一起形成环。 这些化合物是PPAR-γ受体的高选择性激动剂或PPAR-γ受体激动剂的前药。 因此,这些化合物可用于治疗II型糖尿病(NIDDM)。