Synthesis and hypolipidemic activities of 5-thienyl-4-oxazoleacetic acid derivatives.
A series of 2,5-disubstituted 4-oxazoleacetic acid derivatives was synthesized and evaluated for hypolipidemic activity. Among them, those with a thienyl group at C-5 of the oxazole ring exerted highly potent hypolipidemic effects in rats. 2-(4-Fluorophenyl)-5-(3-thienyl)-4-oxazoleacetic acid (88) was the most potent derivative: it was about 2 times as active in normal SD male rats and about 4 times as active in hereditary hyperlipidemic rats (THLR/1) as clofibrate with an improved antiarteriosclerosis index (HDL-Cho/Total-Cho). In addition, it showed inhibition of platelet aggregation ex vivo.
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis; D002994:Clofibrate / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000138:chemical synthesis*; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D000960:Hypolipidemic Agents; D010080:Oxazoles; D014280:Triglycerides; D002994:Clofibrate