The Design, Synthesis, and Antiviral Activity of 4′-Azidocytidine Analogues against Hepatitis C Virus Replication: The Discovery of 4′-Azidoarabinocytidine
David B. Smitha, Genadiy Kalayanova, Christian J. Sunda, Anna Winqvista, Pedro Guilherme Lacerda Ferreira Pinhoa, Tatiana V. Maltsevaa, Véronique Morissona, Vincent Lévêquea, Sonal Rajyagurua, Sophie Le Pogama, Isabel Nájeraa, Kurt Benkestocka, Xiaoxiong Zhoua, Hans Maaga, Nick Cammacka, Joseph A. Martina, Steven Swallowa, Nils Gunnar Johanssona, Klaus Klumppa, Mark A. Smitha✉
- aRoche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, Medivir AB, Department of Medicinal Chemistry, Lunastigen 7, SE-141 44 Huddinge, Sweden
- ✉Corresponding author
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Abstract
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 IC(50) of 0.17 microM in the genotype 1b subgenomic replicon system. The structure-activity relationships within this series of nucleoside analogues are discussed.
TL;DRThe synthesis and biological evaluation of several derivatives of 4'-azidocytidine by varying the substituents at the ribose 2' and 3'-positions are described. (Semantic Scholar)