Hexahydro-pyrrolo- and hexahydro-1 H-pyrido[1,2- b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase

Abstract

Hexahydro-pyrrolo- and hexahydro-1 H-pyrido[1,2- b]pyridazin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Among these, compound 4c displayed potent inhibitory activities in biochemical and replicon assays (IC 50 (1b) <10 nM; EC 50 (1b) = 34 nM) as well as good stability towards human liver microsomes (HLM t 1/2 = 59 min).