Dibasic benzo [b] thiophene derivatives as a novel class of active site directed thrombin inhibitors: 4. SAR studies on the conformationally restricted C3-side chain of …

…, JR McCowan, GF Smith, DS Gifford-Moore

Index: Takeuchi, Kumiko; Kohn, Todd J.; Sall, Daniel J.; Denney, Michael L.; McCowan, Jefferson R.; Smith, Gerry F.; Gifford-Moore, Donetta S. Bioorganic and Medicinal Chemistry Letters, 1999 , vol. 9, # 5 p. 759 - 764

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Citation Number: 40

Abstract

A novel series of benzo [b] thiophene diamine thrombin inhibitors with a conformationally restricted C3-side chain 3 was investigated. The constrained C3-side chain by a cyclohexyl ring contributed to not only an additive but also a synergistic effect on the thrombin inhibitory activity. The SAR studies resulted in the discovery of a potent thrombin inhibitor 27 that was over 750-fold more potent than the initial lead compound 1.