About this eBook
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.
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