Pyrrolo[1,2-b]pyridazin-2-ones as potent inhibitors of HCVNS5B polymerase

Pyrrolo[1,2-b]pyridazin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Structure-based design led to the discovery of compound 3k, which displayed potent inhibitory activities in biochemical and replicon assays (IC50 (1b) < 10 nM; EC50 (1b) = 12 nM) as well as good stability towards human liver microsomes (HLM t(1/2) > 60 min). (C) 2008 Elsevier Ltd. All rights reserved.