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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, 00:00 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.