4-(1,1-Dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-5-hydroxy-2H-pyridazin-3-ones as potent inhibitors of HCV NS5B polymerase

Abstract: 4-(1,1-Dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-5-hydroxy-2H-pyridazin-3-one analogs were discovered as a novel class of inhibitors of HCV NS5B polymerase. Structure-based design led to the identification of compound 3a that displayed potent inhibitory activities in biochemical and replicon assays (1b IC50 <10 nM; 1b EC50 =1.1nM) as well as good stability toward human liver microsomes (HLM t 1/2 >60min). [Copyright &y& Elsevier]