1. Synthesis and biological evaluation of novel propylamine derivatives as orally active squalene synthase inhibitors.
- Author
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Ishihara T, Kakuta H, Moritani H, Ugawa T, and Yanagisawa I
- Subjects
- Administration, Oral, Animals, Cell Line, Drug Evaluation, Preclinical methods, Enzyme Inhibitors administration & dosage, Farnesyl-Diphosphate Farnesyltransferase metabolism, Humans, Male, Propylamines administration & dosage, Rats, Rats, Inbred F344, Rats, Sprague-Dawley, Enzyme Inhibitors chemical synthesis, Farnesyl-Diphosphate Farnesyltransferase antagonists & inhibitors, Propylamines chemical synthesis
- Abstract
Squalene synthase inhibitors are potentially superior hypolipidemic agents. We synthesized novel propylamine derivatives, as well as evaluated their ability to inhibit squalene synthase and their lipid-lowering effects in rats. 1-Allyl-2-[3-(benzylamino)propoxy]-9H-carbazole (YM-75440) demonstrated potent inhibition of the enzyme derived from HepG2 cells with an IC(50) value of 63 nM. It significantly reduced both plasma total cholesterol and plasma triglyceride levels following oral dosing to rats with a reduced tendency to elevate plasma transaminase levels.
- Published
- 2004
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