Design and synthesis of potent and selective 5,6-fused heterocyclic thrombin inhibitors

Abstract Thrombin, a serine protease, phays a central role in the initiation of thrombotic events. We report the design, synthesis, and antithrombotic efficacy of XU817 ( 7 ), a nonpeptide 5-(amidino) indole thrombin inhibitor. Utilizing the co-crystal structure of XU817 bound in the active site of thrombin we were able to synthesize analogs with enhanced thrombin affinity.