Synthesis and biological evaluation of novel dabigatran derivatives as thrombin inhibitors

Abstract

A novel series of 3-[{2-[(4-carbamimidoylphenylamino)methyl]-1-substituted-1H-benzoimidazole-5-carbonyl}(3-chloro-4-fluorophenyl)amino]propionic derivatives of dabigatran was synthesized. The structures of the compounds were characterized by 1H NMR, 13C NMR, HRMS, and elemental analysis. The compounds were screened for in vitro thrombin inhibitory activity. The results indicated that the compounds had low to moderate inhibitory activity. The compounds with N-methyl and N-ethyl side chains had much greater inhibitory activity against thrombin than those with other side chains.