title: Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions.
abstract: 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.
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, Jilin University, 75 Haiwai Street, Changchun, Jilin 130012, PR China.
authors.forename: Xianxiu
authors.initials: X
authors.lastname: Xu
authors.forename: Renzhong
authors.initials: R
authors.lastname: Fu
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Shengwu
authors.initials: S
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Bai
mesh_terms: 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
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D002791:Cholesterol, Dietary; D000069438:Ezetimibe