Orally efficacious thrombin inhibitors with cyanofluorophenylacetamide as the P2 motif

Abstract 2-Cyano-6-fluorophenylacetamide was explored as a novel P2 scaffold in the design of thrombin inhibitors. Optimization around this structural motif culminated in 14 , which is a potent thrombin inhibitor ( K i  = 1.2 nM) that exhibits robust efficacy in canine anticoagulation and thrombosis models upon oral administration.