Wonsuk Chang, Donghui Bao, Byoung-Kwon Chun, Devan Naduthambi, Dhanapalan Nagarathnam, Suguna Rachakonda, P Ganapati Reddy, Bruce S Ross, Hai-Ren Zhang, Shalini Bansal, Christine L Espiritu, Meg Keilman, Angela M Lam, Congrong Niu, Holly Micolochick Steuer, Phillip A Furman, Michael J Otto, Michael J Sofia
Hepatitis C virus afflicts approximately 180 million people worldwide, and the development of direct acting antivirals may offer substantial benefit compared to the current standard of care. Accordingly, prodrugs of 2'-deoxy-2'-fluoro-2'-C-methylguanosine monophosphate analogues were prepared and evaluated for their anti-HCV efficacy and tolerability. These prodrugs demonstrated >1000 fold greater potency than the parent nucleoside in a cell-based replicon assay as a result of higher intracellular triphosphate levels...
February 10, 2011: ACS Medicinal Chemistry Letters