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 phenylpyridyl 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 the mouse liver. The compounds with an oxetane, cyclobutanone or gamma-butyrolactone ring as isosters of a 2-oxetanone ring were entirely inactive. Among sythetic analogs, anti-4-[3-[2-(5-isopropyl-2-pyridyl)-ethyl]-phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (10b) was most active in vitro. The structure-activity relationships on the transformations of 2-oxetanone and its side chain were obtained.