391687-64-2Relevant articles and documents
Discovery of a novel acyl-CoA: Cholesterol acyltransferase inhibitor: The synthesis, biological evaluation, and reduced adrenal toxicity of (4-phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety
Ogino, Masaki,Nakada, Yoshihisa,Negoro, Nobuyuki,Itokawa, Shigekazu,Nishimura, Satoshi,Sanada, Tsukasa,Satomi, Tomoko,Kita, Shunbun,Kubo, Kazuki,Marui, Shogo
, p. 1369 - 1375 (2012/01/02)
As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine) acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl) phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.
COUMARIN DERIVATIVES, PROCESS FOR THEIR PRODUCTION AND USE THEREOF
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Page 38; 39, (2010/02/08)
Compounds represented by the general formula [I]: wherein R1 and R2 are each hydrogen, halogen, an optionally substituted linear hydrocarbon group, or hydroxyl which may be substituted with an optionally substituted liner hydrocarbon
