Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions.
The underlying principle of drug design in this paper is that the maximum retention of the functional groups that exist in the marketed drug would provide a higher probability for comparable safety while the conformational changes in the newly created analogs should not constitute a significant structural variation to adversely affect biological activity. Four individual isomers of backbone re-organized ezetimibe analogs were designed and synthesized. Their effects on the cholesterol levels in rat serum were evaluated by a high-cholesterol and high-fat diet feeding experiment. All the new analogs showed significant effect in lowering the levels of total cholesterol in serum.
Xu
Xianxiu
X
The Center for Combinatorial Chemistry and Drug Discovery, Jilin University, 75 Haiwai Street, Changchun, Jilin 130012, PR China.
Fu
Renzhong
R
Chen
Jin
J
Chen
Shengwu
S
Bai
Xu
X
D000042:Absorption / Q000187:drug effects; D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001384:Azetidines / Q000737:chemistry*; D002791:Cholesterol, Dietary / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D018360:Crystallography, X-Ray; D004036:Diet, Atherogenic; D015195:Drug Design; D000069438:Ezetimibe; D015394:Molecular Structure; D051381:Rats; D013237:Stereoisomerism
D000924:Anticholesteremic Agents; D001384:Azetidines; D002791:Cholesterol, Dietary; D000069438:Ezetimibe