| 摘要 |
5-(Cyclo)alkoxy-3-(substituted phenyl)-3H-1,3,4-oxadiazol-2-one derivatives (I) are new. Oxadiazolone derivatives of formula (I) and their salts and acid addition salts are new. [Image] R 11-6C alkyl or 3-9C cycloalkyl (both optionally substituted (os) by one or more of phenyl (itself os by 1-3 of halo, T, OT, NO 2 or CF 3), OT, ST or NT 2); T : 1-4C alkyl; R 2-R 5H, halo, NO 2, T or 1-9C alkoxy, (6-10C) aryl-(1-4C) alkoxy, 6-10C aryloxy, 6-10C aryl, 3-8C cycloalkyl or 3-8C cycloalkoxy (all os by 1-3 of halo, CF 3, OT or T), or 2-oxo-pyrrolidin-1-yl, 2,5-dimethyl-pyrrol-1-yl or -N(R 6)-AR 7; R 6H, T or (6-10C) aryl-(1-4C) alkyl (os by halo, CF 3, 1-8C alkoxy or T); A : direct bond, CO n, SO n or CONH; n : 1 or 2; R 7H, or 1-18C alkyl or 2-18C alkenyl (both os by 1-3 of T, halo, CF 3, OT, NT 2, COOH, COOT, 6-12C aryl, 6-12C aryloxy, 6-12C arylcarbonyl, (6-10C) aryl-(1-4C) alkoxy or oxo (where aryl moieties are os by halo, T, SO 2NH 2 or SMe)), (6-10C) aryl-(1-4C) alkyl, (5-8C) cycloalkyl-(1-4C) alkyl, 5-8C cycloalkyl, (6-10C) aryl-(2-6C) alkenyl, 6-10C aryl, diphenyl, diphenyl-(1-4C) alkyl or indanyl (all os by 1 or 2 of 1-18C alkyl, 1-18C alkoxy, 3-8C cycloalkyl, COOH, OH, COT, (6-10C) aryl-(1-4C) alkyl, (6-10C) aryl-(1-4C) alkoxy, 6-10C aryloxy, NO 2, CN, 6-10C aryl, SO 2F, (1-6C) alkoxycarbonyl, 6-10C arylsulfonyloxy, pyridyl, 6-10C arylsulfonylamino, halo, CF 3 or OCF 3, where alkyl is os by COOT, CF 3 or COOH and aryl is os by halo, CF 3 or OT); or -CH 2) r-Het; r : 0-3; Het : optionally benzo-fused, saturated or unsaturated 5-7 membered heterocycle (os by T, 6-10C aryl, halo, OT, COOT, (6-10C) aryl-(1-4C) alkyl, (6-10C) aryl-(1-4C) alkylthio or NO 2, where the fused benzo ring is os by halo, OT or CF 3 and alkyl in aralkyl is os by OMe or CF 3); provided that at least one of R 2-R 5 is 2-oxo-pyrrolidin-1-yl, 2,5-dimethyl-pyrrol-1-yl or -N(R 6)-AR 7. An independent claim is also included for the preparation of (I). - ACTIVITY : Antidiabetic. - MECHANISM OF ACTION : Hormone-sensitive lipase (HSL) inhibitor. 5-Methoxy-3-(2-chloro-4-(4- heptyl-benzoylamino)-phenyl)-3H-1,3,4-oxadiazol-2-one (Ia) displayed an IC 50 value of 0.02 MicroM for inhibition of HSL.
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