Design and synthesis of potent and selective 5,6-fused heterocyclic thrombin inhibitors
C Dominguez1, D E Duffy, Q Han
1DuPont Pharmaceuticals Company, Wilmington, DE 19880-0500, USA.
Bioorganic & Medicinal Chemistry Letters
|May 7, 1999
Abstract:
Thrombin, a serine protease, plays 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.


