Synthesis of 3-ureido derivatives of coumarin and 2-quinolone as potent acyl-CoA: cholesterol acyltransferase inhibitors.
Novel 3-ureido derivatives of 4-phenylcoumarin and 4-phenyl-2-quinolone were synthesized and evaluated for acyl-CoA: cholesterol acyltransferase (ACAT)-inhibitory activity. These derivatives inhibited rat intestinal ACAT with IC50 values at the 10(-8) to 10(-9) M level and were found to normalize plasma cholesterol levels in cholesterol-fed rats when administered as dietary admixtures.
Tawada
H
H
Pharmaceutical Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan.
Natsugari
H
H
Ishikawa
E
E
Sugiyama
Y
Y
Ikeda
H
H
Meguro
K
K
D000818:Animals; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
C094410:4-phenylquinolone; D003374:Coumarins; D000960:Hypolipidemic Agents; D015363:Quinolones; C094411:4-phenylcoumarin; D002785:Sterol O-Acyltransferase