To mimic the folded side chain conformation of 1233A (1), which is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitor, 1233A analogs with aromatic rings in the side chain were synthesized. The 2-oxetanone moiety was kept intact. Among 1233A and its synthetic analogs, trans-3-hydroxymethyl-4-[2-(7-methoxycarbonyl-l-naphthyl)ethyl]-2-oxetanone (23) showed the highest HMG-CoA synthase inhibitory activity in vitro. The structure-activity relationship at the side chain is discussed.
- 1233A analog
- 3-hydroxy-3-methylglutaryl coenzyme A synthase
- cholesterol biosynthesis
- structure-activity relationship
ASJC Scopus subject areas
- Drug Discovery