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The discovery of fluoropyridine-based inhibitors of the Factor VIIa/TF complex |
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| Authors: | Kohrt Jeffrey T Filipski Kevin J Cody Wayne L Cai Cuiman Dudley Danette A Van Huis Chad A Willardsen J Adam Rapundalo Stephen T Saiya-Cork Kamlai Leadley Robert J Narasimhan Lakshmi Zhang Erli Whitlow Marc Adler Marc McLean Kirk Chou Yuo-Ling McKnight Cecile Arnaiz Damian O Shaw Kenneth J Light David R Edmunds Jeremy J |
| Institution: | Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. jeffrey.kohrt@pfizer.com |
| Abstract: | 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. |
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