Mechanism-based thrombin inhibitors: design, synthesis, and molecular docking of a new selective 2-oxo-2H-1-benzopyran derivative.
(2007) Journal of Medicinal Chemistry — Vol. 50, n° 15, p. 3645-3650 (2007)
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- Authors
Robert, S. 
- Abstract
- New 2-oxo-2H-1-benzopyran derivatives were prepared to optimize 2a,b, initially developed as mechanism-based alpha-chymotrypsin (alpha-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 (ki/KI = 3455 M(-1) x s(-1)), displaying an excellent selectivity profile against other serine proteases such as factor Xa, trypsin, and alpha-CT. Docking analysis of this compound into the different protein structures revealed the molecular basis responsible for its potency and selectivity.
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Citations
Frédérick, R., Robert, S., Charlier, C., Wouters, J., Masereel, B., & Pochet, L. (2007). Mechanism-based thrombin inhibitors: design, synthesis, and molecular docking of a new selective 2-oxo-2H-1-benzopyran derivative. Journal of Medicinal Chemistry, 50(15), 3645-3650. https://doi.org/10.1021/jm061368v (Original work published 2007)