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Bioorg Med Chem Lett. 2013 Aug 1;23(15):4367-9. doi: 10.1016/j.bmcl.2013.05.078. Epub 2013 Jun 4.

High potency improvements to weak aryl uracil HCV polymerase inhibitor leads.

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  • 1AbbVie, Department R4AJ, Building AP52N, 1 North Waukegan Road, North Chicago, IL 60064, United States. pamela.l.donner@abbvie.com

Abstract

Described herein is the development of a potent non-nucleoside, small molecule inhibitor of genotype 1 HCV NS5B Polymerase. A 23 μM inhibitor that was active against HCV polymerase was further elaborated into a potent single-digit nanomolar inhibitor of HCV NS5B polymerase by additional manipulation of the R and R1 substituents. Subsequent modifications to improve physical properties were made in an attempt to achieve an acceptable pharmacokinetic profile.

Copyright © 2013. Published by Elsevier Ltd.

PMID:
23791079
[PubMed - indexed for MEDLINE]
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