Ezetimibe and other azetidinone cholesterol absorption inhibitors.
Atherosclerotic coronary artery disease remains a major healthcare concern especially in developed countries. While lowering plasma cholesterol levels via diet, exercise, and pharmacotherapy can reduce this risk of developing coronary artery disease, there remains a need for more effective drug therapies. The azetidinone cholesterol absorption inhibitors typified by ezetimibe represent the first new approach to lipid lowering therapy in more than a decade. This review summarizes the medicinal chemistry of the azetidinone cholesterol absorption inhibitors as a class, with emphasis on factors that contributed both to the discovery of ezetimibe as well as to our overall understanding of S.A.R. trends in this area.
Clader
John W
JW
Department of Cardiovascular and CNS Medicinal Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-1300, USA. john.clader@spcorp.com
D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001384:Azetidines / Q000494:pharmacology* / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D003327:Coronary Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000924:Anticholesteremic Agents; D001384:Azetidines; D002784:Cholesterol; D000069438:Ezetimibe