Design and biological evaluation of a series of thiophene-based 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors

Abstract A series of highly functionalized thiophene-based 3,5-dihydroxyheptenoic acid derivatives ( 10 ) were prepared from aldehydes 6 by homologation, aldol condensation with ethyl acetoacetate dianion and stereoselective β-hydroxyketone reduction. High levels of HMG-CoA reductase inhibitory activity have been found within the series. The most active analog in vitro was 10i whereas in vivo, 10e , 10i , 10m , 10n , 10o , and 10v were approximately equipotent.