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

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Abstract

Hexahydro-pyrrolo- and hexahydro-1H-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 (IC50 (1b) <10 nM; EC50 (1b) = 34 nM) as well as good stability towards human liver microsomes (HLM t1/2 = 59 min).

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Acknowledgments

The authors thank Drs. Peter Dragovich, Devron Averett and Steve Worland for their support and helpful discussions during the course of this work.

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