Synthesis and structure-activity relationship studies on a novel series of naphthylidinoylureas as inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT).
The synthesis and structure-activity relationships of N-phenyl-N'-[3-(4-phenylnaphthylidinoyl)]urea derivatives 3 as a novel structural class of potent ACAT inhibitors is described. A 3-methoxy group substituted on the naphthylidinone 4-phenyl ring, together with a 1-N-(n)butyl substitution, SM-32504 (3m), gave a potent ACAT inhibitor, in vitro, respectively. The most potent compound, SM-32504 (3m), decreased the serum cholesterol level significantly in a high fat and high cholesterol-fed mouse model.
Research Division, Sumitomo Pharmaceuticals Co. Ltd, 1-98 Kasugade Naka 3-chome, Konohana-ku, Osaka 554-0022, Japan. ohnuma@sumitomopharm.co.jp
Satoshi
S
Ohnuma
Masami
M
Muraoka
Katsuhisa
K
Ioriya
Naohito
N
Ohashi
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014508:Urea; D002785:Sterol O-Acyltransferase