COUMARIN DERIVATIVES, PROCESS FOR THEIR PRODUCTION AND USE THEREOF

摘要

Coumarin derivatives (I) are new. Coumarin derivatives of formula (I) and their salts are new; [Image] R 1, R 2H, halo, Q, OH or OQ; Q : optionally substituted linear hydrocarbyl; or CR 1CR 2optionally substituted carbocyclyl or dihydrofuran (optionally substituted by oxo); A : phenyl substituted by XY and optionally further substituted; B : optionally substituted aromatic X : bond or spacer have 1-6 atoms in chain; Y : optionally esterified carboxy, CN or optionally substituted carbamoyl or heterocyclyl; Provided that the following compounds are excluded: (1) 3-[3-[7-chloro-3-(2-[[4-chloro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]-2-propionic acid; (2) ethyl 3-[3-[7-chloro-3-(2-[[4-chloro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]-2-propionoate; (3) methyl (2E)-3-[3-[7-chloro-3-(2-[[4-chloro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]propenoate; (4) (2E)-3-[3-[7-chloro-3-(2-[[4-chloro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]-2-propenoic acid; (5) ethyl (2E)-3-[3-[7-chloro-3-(2-[[4-chloro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]-2-propanoate; (6) ethyl (2E)-3-[3-[7-chloro-3-(2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]-2-propanoate; and (7) (2E)-3-[3-[7-chloro-3-(2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl)-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]-2-propanoic acid. ACTIVITY : Cardiant; Antianginal; Vasotropic; Antiipemic; Cerebroprotective; Neuroprotective; Nootropic. MECHANISM OF ACTION : HMG-CoA-Reductase-Inhibitor; ACAT-Inhibitor. In assays using murine peritoneal macrophage microsomes a compound of formula (Ia) has an IC 5 0 value for ACAT activity of 0.43 MicroM.