Synthesis and evaluation of S -4-(3-thienyl)phenyl-α-methylacetic acid

Abstract

Herein we report an efficient procedure to synthesize S-4-(3-thienyl)phenyl-α-methylacetic acid, an enantiomerically pure intermediate of a recently approved nonsteroidal antiinflammatory cyclooxygenase inhibitor, atliprofen [methyl RS-4-(3-thienyl)phenyl-α-methylacetate]. The interactions of the active S-isomer of the acid were theoretically compared with those of S-ibuprofen through molecular docking studies using COX-1 and COX-2 protein structures. The results were corroborated by in vitro and in vivo studies. An efficient process for the preparation of S-4-(3-thienyl)phenyl-α-methylacetic acid, an enantiomerically pure intermediate of recently approved NSAID atliprofen is reported. The pharmacologically active isomer, S-4-(3-thienyl)phenyl-α-methylacetic acid was compared with S-ibuprofen by docking studies on COX enzyme structures followed by biological evaluations.