Synthesis, biological profile, and quantitative structure-activity relationship of a series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors

…, I Motoc, W Han, N Balasubramanian…

Index: Sit; Parker; Motoc; Han; Balasubramanian; Catt; Brown; Harte; Thompson; Wright Journal of Medicinal Chemistry, 1990 ,  vol. 33,  # 11  p. 2982 - 2999

Full Text: HTML

Citation Number: 75

Abstract

A series of 9, 9-bis (4-fluorophenyl)-3, 5-dihydroxy-8-(alkyltetrazol-5-yl)-6, 8-nonadienoic acid derivatives 1 were synthesized and found to inhibit competitively the enzyme 3-hydroxy- 3-methylglutaryl coenzyme A (HMG-CoA) reductase. The analogues having IN- methyltetrazol-5-yl attached to the C8-position (3a, 4a, R'= R2= F) are the most active in suppressing cholesterol biosynthesis in both in vitro and in vivo models: the ICs for the ...