Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: potent acyl-CoA:cholesterol acyltransferase inhibitor with improved aqueous solubility.
4-Aryl-1,8-naphthyridin-2(1H)-on-3-yl urea derivatives with hydrophilic groups were synthesized in order to improve aqueous solubility and pharmacokinetic property. SMP-797 possessing (4-aminophenyl)ureido and 3-(hydroxypropoxyphenyl) moieties showed potent ACAT inhibitory activity and excellent oral efficacy.
Ban
Hitoshi
H
Research Division, Sumitomo Pharmaceuticals Co., Ltd 1-98, Kasugadenaka 3-chome, Konohana-ku, Osaka 554-0022, Japan. ban@sumitomopharm.co.jp
Muraoka
Masami
M
Ioriya
Katsuhisa
K
Ohashi
Naohito
N
D000217:Acyltransferases / Q000737:chemistry; D000284:Administration, Oral; D000924:Anticholesteremic Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D013696:Temperature; D013997:Time Factors; D014508:Urea / Q000031:analogs & derivatives*
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D009287:Naphthyridines; C508738:SMP-797; D014508:Urea; D000217:Acyltransferases; D002785:Sterol O-Acyltransferase