Orally efficacious thrombin inhibitors with cyanofluorophenylacetamide as the P2 motif

…, V Mohan, C Crysler, S Eisennagel, M Dasgupta…

文献索引：Kreutter, Kevin D.; Lu, Tianbao; Lee, Lily; Giardino, Edward C.; Patel, Sharmila; Huang, Hui; Xu, Guozhang; Fitzgerald, Mark; Haertlein, Barbara J.; Mohan, Venkatraman; Crysler, Carl; Eisennagel, Stephen; Dasgupta, Malini; McMillan, Martin; Spurlino, John C.; Huebert, Norman D.; Maryanoff, Bruce E.; Tomczuk, Bruce E.; Damiano, Bruce P.; Player, Mark R. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 9 p. 2865 - 2870

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被引用次数: 16

摘要

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 (Ki= 1.2 nM) that exhibits robust efficacy in canine anticoagulation and thrombosis models upon oral administration.