Synthesis of novel thrombin inhibitors. Use of ring-closing metathesis reactions for synthesis of P2 cyclopentene-and cyclohexenedicarboxylic acid derivatives

F Thorstensson, I Kvarnström, D Musil…

Index: Thorstensson, Fredrik; Kvarnstroem, Ingemar; Musil, Djordje; Nilsson, Ingemar; Samuelsson, Bertil Journal of Medicinal Chemistry, 2003 , vol. 46, # 7 p. 1165 - 1179

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Citation Number: 29

Abstract

The thrombin inhibitory tripeptide d-Phe-Pro-Arg has been mimicked using either cyclopentenedicarboxylic derivatives or a cyclohexenedicarboxylic derivative as surrogate for the P2 proline. In the P3 position, tertiary amides were optimized as d-Phe P3 replacements. The P1 arginine was, in all compounds, substituted with the more rigid and biocompatible 4-aminomethylbenzamidine. One of the novel inhibitors was cocrystallized ...