| Abstract
| - In our search for new therapeutic agents against chronic hepatitis C, a ribonucleoside analogue,2‘-C-methylcytidine, was discovered to be a potent and selective inhibitor in cell culture of a number ofRNA viruses, including the pestivirus bovine viral diarrhea virus, a surrogate model for hepatitis C virus(HCV), and three flaviviruses, namely, yellow fever virus, West Nile virus, and dengue-2 virus. However,pharmacokinetic studies revealed that 2‘-C-methylcytidine suffers from a low oral bioavailability. To overcomethis limitation, we have synthesized the 3‘-O-l-valinyl ester derivative (dihydrochloride form, valopicitabine,NM283) of 2‘-C-methylcytidine. We detail herein for the first time the chemical synthesis and physicochemicalcharacteristics of this anti-HCV prodrug candidate, as well as a comparative study of its pharmacokineticparameters with those of its parent nucleoside analogue, 2‘-C-methylcytidine.
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