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The Design, Synthesis, and Antiviral Activity of 4′-Azidocytidine Analogues against Hepatitis C Virus Replication: The Discovery of 4′-Azidoarabinocytidine

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journal contribution
posted on 08.01.2009 by David B. Smith, Genadiy Kalayanov, Christian Sund, Anna Winqvist, Pedro Pinho, Tatiana Maltseva, Veronique Morisson, Vincent Leveque, Sonal Rajyaguru, Sophie Le Pogam, Isabel Najera, Kurt Benkestock, Xiao-Xiong Zhou, Hans Maag, Nick Cammack, Joseph A. Martin, Steven Swallow, Nils Gunnar Johansson, Klaus Klumpp, Mark Smith
4′-Azidocytidine 3 (R1479) has been previously discovered as a potent and selective inhibitor of HCV replication targeting the RNA-dependent RNA polymerase of hepatitis C virus, NS5B. Here we describe the synthesis and biological evaluation of several derivatives of 4′-azidocytidine by varying the substituents at the ribose 2′ and 3′-positions. The most potent compound in this series is 4′-azidoarabinocytidine with an IC50 of 0.17 μM in the genotype 1b subgenomic replicon system. The structure−activity relationships within this series of nucleoside analogues are discussed.