Mechanism-based thrombin inhibitors: Design, synthesis, and molecular docking of a new selective 2-oxo-2H-1-benzopyran derivative

Raphaël Frédérick, Séverine Robert, Caroline Charlier, Johan Wouters, Bernard Masereel, Lionel Pochet

Research output: Contribution to journalArticlepeer-review

Abstract

New 2-oxo-2H-1-benzopyran derivatives were prepared to optimize 2a,b, initially developed as mechanism-based α-chymotrypsin (α-CT) inhibitors, into potent and selective thrombin (THR) inhibitors. From this study, 22, characterized by a 2-(N-ethyl-2′-oxoacetamide)-5′- chlorophenyl ester side chain, was shown to be a good THR inhibitor (k i/K I = 3455 M -1·s -1), displaying an excellent selectivity profile against other serine proteases such as factor Xa, trypsin, and α-CT. Docking analysis of this compound into the different protein structures revealed the molecular basis responsible for its potency and selectivity.

Original languageEnglish
Pages (from-to)3645-3650
Number of pages6
JournalJournal of Medicinal Chemistry
Volume50
Issue number15
DOIs
Publication statusPublished - 26 Jul 2007

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