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

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 (IC50 (1b) < 10 nM; IC50 (1a) < 25 nM, EC50 (1b) = 16 nM), good in vitro DMPK properties, as well as moderate oral bioavailability in monkeys (F = 24%).

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