Yellow Fever Research Today is a free monthly online journal that collates and summarizes the latest research about Yellow Fever, including details on immunization, vaccines, symptoms, transmission.

Synthesis and pharmacokinetics of valopicitabine (NM283), an efficient prodrug of the potent anti-HCV agent 2'-C-methylcytidine.

Pierra C, Amador A, Benzaria S, Cretton-Scott E, D'Amours M, Mao J, Mathieu S, Moussa A, Bridges EG, Standring DN, Sommadossi JP, Storer R, Gosselin G

Laboratoire Coopératif Idenix-CNRS-Université Montpellier II, Case Courrier 008, Université Montpellier II, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.

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 of RNA 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 overcome this 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 physicochemical characteristics of this anti-HCV prodrug candidate, as well as a comparative study of its pharmacokinetic parameters with those of its parent nucleoside analogue, 2'-C-methylcytidine.

Published 26 October 2006 in J Med Chem, 49(22): 6614-20.
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