1994 Volume 42 Issue 6 Pages 1272-1278
Isosteric side chain analogs of 3a were synthesized and tested for inhibitory activivies towards 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and upon cholesterol production in Hep G2 cells and in mouse liver. It became clear that the lipophilic substituent on the aromatic ring and the terminal hydrophilic group in the side chain were important in the enhancement of activity. 4-[2-(3-n-Hexyloxyphanyl)ethyl]-3-hydroxymethyl-2-oxetanone (5a) showed equivalent inhibitory activity in vivo to that of 1233A.