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Bioorg Med Chem Lett. 2009 Jul 1;19(13):3642-6. doi: 10.1016/j.bmcl.2009.05.004. Epub 2009 May 7.

Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure-activity relationships of benzothiazine-substituted quinolinediones.

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  • 1Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.


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.

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