Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position.

Abstract Thrombin inhibitors incorporating o -aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the α-thrombin–hirugen complex provides an explanation for these unanticipated results.