Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 19, Issue 13, Pages 3642-3646Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.05.004
Keywords
Non-nucleoside inhibitors; HCV polymerase NS5B; Benzothiazine; Pharmacokinetic studies; DMPK properties; X-ray co-crystal structures
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A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase. (C) 2009 Elsevier Ltd. All rights reserved.
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