1372178-18-1Relevant articles and documents
Discovery of a potent and orally available acyl-CoA: Cholesterol acyltransferase inhibitor as an anti-atherosclerotic agent: (4-Phenylcoumarin) acetanilide derivatives
Ogino, Masaki,Fukui, Seiji,Nakada, Yoshihisa,Tokunoh, Ryosuke,Itokawa, Shigekazu,Kakoi, Yuichi,Nishimura, Satoshi,Sanada, Tsukasa,Fuse, Hiromitsu,Kubo, Kazuki,Wada, Takeo,Marui, Shogo
body text, p. 1268 - 1273 (2011/11/06)
Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified. Evaluation of the structure-activity relationships of a substituent on this scaffold, with an emphasis on improving the pharmacokinetic profile led to the discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3- yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice. Compound 23 also showed regressive effects on atherosclerotic plaques in apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os ( p.o.).
