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

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

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.

langue originaleAnglais
Pages (de - à)3645-3650
Nombre de pages6
journalJournal of Medicinal Chemistry
Volume50
Numéro de publication15
Les DOIs
étatPublié - 26 juil. 2007

Empreinte digitale

Benzopyrans
Thrombin
Derivatives
Factor Xa
Chymotrypsin
Serine Proteases
Molecular Structure
Trypsin
Esters
Proteins

Citer ceci

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title = "Mechanism-based thrombin inhibitors: Design, synthesis, and molecular docking of a new selective 2-oxo-2H-1-benzopyran derivative",
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.",
author = "Rapha{\"e}l Fr{\'e}d{\'e}rick and S{\'e}verine Robert and Caroline Charlier and Johan Wouters and Bernard Masereel and Lionel Pochet",
year = "2007",
month = "7",
day = "26",
doi = "10.1021/jm061368v",
language = "English",
volume = "50",
pages = "3645--3650",
journal = "J. Med. Chem.",
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publisher = "American Chemical Society",
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T1 - Mechanism-based thrombin inhibitors

T2 - Design, synthesis, and molecular docking of a new selective 2-oxo-2H-1-benzopyran derivative

AU - Frédérick, Raphaël

AU - Robert, Séverine

AU - Charlier, Caroline

AU - Wouters, Johan

AU - Masereel, Bernard

AU - Pochet, Lionel

PY - 2007/7/26

Y1 - 2007/7/26

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AB - 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.

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DO - 10.1021/jm061368v

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