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

Abstract 5,6-Dihydro-1 H -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)  50 (1a)  50 (1b) = 16 nM), good in vitro DMPK properties, as well as moderate oral bioavailability in monkeys ( F  = 24%).