… [b] thiophene derivatives as a novel class of active site directed thrombin inhibitors. 5. Potency, efficacy, and pharmacokinetic properties of modified C-3 side chain …

…, DD Giera, DS Gifford-Moore, RW Harper…

Index: Sall, Daniel J.; Bailey, Dianna L.; Bastian, Jolie A.; Buben, John A.; Chirgadze, Nickolay Y.; Clemens-Smith, Amy C.; Denney, Michael L.; Fisher, Matthew J.; Giera, Deborah D.; Gifford-Moore, Donetta S.; Harper, Richard W.; Johnson, Lea M.; Klimkowski, Valentine J.; Kohn, Todd J.; Lin, Ho-Shen; McCowan, Jefferson R.; Palkowitz, Alan D.; Richett, Michael E.; Smith, Gerald F.; Snyder, David W.; Takeuchi, Kumiko; Toth, John E.; Zhang, Minsheng Journal of Medicinal Chemistry, 2000 , vol. 43, # 4 p. 649 - 663

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Citation Number: 47

Abstract

A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit 1a led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271× 106 L/mol, respectively) represent 2200-and 2900- fold increases in potency over the starting lead 1a. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of ...