The discovery of fluoropyridine-based inhibitors of the Factor VIIa/TF complex

Autor:	Chad A. Van Huis, Jeremy J. Edmunds, Kenneth J. Shaw, Marc Whitlow, Arnaiz Damian O, Marc Adler, Cuiman Cai, David R. Light, Kamlai Saiya-Cork, J. Adam Willardsen, Lakshmi Narasimhan, Erli Zhang, Stephen T. Rapundalo, Kevin J. Filipski, Wayne L. Cody, Kirk Mclean, Danette Dudley, Jeffrey T. Kohrt, Cecile McKnight, Robert J. Leadley, Yuo-Ling Chou
Rok vydání:	2005
Předmět:	Enzyme complex Hydroxybenzoic acid medicine.drug_mechanism_of_action Pyridines Stereochemistry Clinical Biochemistry Factor Xa Inhibitor Pharmaceutical Science Factor VIIa Crystallography X-Ray Biochemistry Thromboplastin Inhibitory Concentration 50 Structure-Activity Relationship Tissue factor Fibrinolytic Agents Drug Discovery medicine Humans Enzyme Inhibitors Binding site Molecular Biology Binding Sites biology Chemistry Organic Chemistry Active site Protease inhibitor (biology) Enzyme inhibitor Prothrombin Time biology.protein Molecular Medicine Factor Xa Inhibitors Protein Binding medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 15:4752-4756
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2005.07.059
Popis:	The activated Factor VII/tissue factor complex (FVIIa/TF) plays a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. An X-ray crystal structure of a fluoropyridine-based FVIIa/TF inhibitor bound in the active site of the enzyme complex suggested that incorporation of substitution at the 5-position of the hydroxybenzoic acid side chain could lead to the formation of more potent inhibitors through interactions with the S1'/S2' pocket.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f2c6b0dc75cebe92a561353096bd522 https://doi.org/10.1016/j.bmcl.2005.07.059 Zobrazit plný text záznamu Full Text from ScienceDirect