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

Article abstract of DOI:10.1016/S0960-894X(99)00113-4

Thrombin, a serine protease, plays a central role in the initiation of thrombotic events. We report 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.