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Bioorg Med Chem Lett. 2009 Jan 15;19(2):451-8. doi: 10.1016/j.bmcl.2008.11.048. Epub 2008 Nov 18.

5,6-Dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase.

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  • 1Department of Medicinal Chemistry, Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA. fruebsam@anadyspharma.com


5,6-Dihydro-1H-pyridin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Among these, compound 4ad displayed potent inhibitory activities in biochemical and replicon assays (IC(50) (1b)<10nM; IC(50) (1a)<25nM, EC(50) (1b)=16nM), good in vitro DMPK properties, as well as moderate oral bioavailability in monkeys (F=24%).

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