SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF NEW HMG-COA SYNTHASE INHIBITORS - 2-OXETANONES WITH A SIDE-CHAIN CONTAINING BIPHENYL, TERPHENYL OR PHENYLPYRIDINE

A series of 1233A analogs containing biphenylyl, terphenylyl or phenyl pyridyl groups in their side chain were synthesized and tested for the inhibitory activities against 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA) synthase and inhibition for the cholesterol biosynthesis in t he mouse liver. The compounds with an oxetane, cyclobutanone or gamma- butyrolactone ring as isosters of a 2-oxetanone ring were entirely ina ctive. Among sythetic analogs, )-ethyl]-phenyl]ethyl]-3-hydroxymethyl- 2-oxetanone (10b) was most active in vitro. The structure-activity rel ationships on the transformations of 2-oxetanone and its side chain we re obtained.