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7216355 
Journal Article 
Discovery of the cholesterol absorption inhibitor, ezetimibe 
Genellin, CR; , 
2013 
ELSEVIER ACADEMIC PRESS INC 
SAN DIEGO 
INTRODUCTION TO BIOLOGICAL AND SMALL MOLECULE DRUG RESEARCH AND DEVELOPMENT: THEORY AND CASE STUDIES 
399-416 
WOS:000337309700016 
A brief introduction to cholesterol and lipoproteins is followed by a short account of the types of drugs which reduce cholesterol levels (bile sequestrants, hypocholesterolaemics, fibrates as acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, statins as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, and saponins). This chapter continues with a background to the extraordinary research effort at the Schering-Plough Research Institute on ACAT inhibitors and the structure activity studies that led to the lead cholesterol absorption inhibitor, the azetidinone SCH 48461. Impressive studies of the metabolism of SCH 48461 and the outstanding application of the results to drug design led to ezetimibe, which was shown to be a potent inhibitor of intestinal cholesterol uptake by a then unknown mechanism. Continued investigation using ezetimibe as a tool culminated in the remarkable discovery of a previously unknown mechanism for cholesterol uptake. 
Cholesterol; Ezetimibe; Fibrates; HMG-CoA reductase; Hypocholesterolaemic drugs; LDL cholesterol; SCH 48461; SCH 58235; Statins; Acyl-coA:cholesterol acyltransferase (ACAT); High-density lipoprotein (HDL); 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA); Intermediate-density lipoprotein (IDL); Low-density lipoprotein (LDL); Niemann-Pick C1-like 1 (NPC1L1); peroxisome proliferator-activated receptor (PPAR-alpha); Very low-density lipoprotein (VLDL) 
Ganellin, R; Roberts, S; Jefferis, R; 
978-0-12-397176-0