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

Smith, David B.; Kalayanov, Genadiy; Sund, Christian; Winqvist, Anna; Pinho, Pedro; Maltseva, Tatiana; Morisson, Veronique; Leveque, Vincent; Rajyaguru, Sonal; Le Pogam, Sophie; Najera, Isabel; Benkestock, Kurt; Zhou, Xiao-Xiong; Maag, Hans; Cammack, Nick; Martin, Joseph A.; Swallow, Steven; Johansson, Nils Gunnar; Klumpp, Klaus; Smith, Mark

doi:10.1021/jm800981y

Research article2009Peer reviewed

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

Smith, David B.; Kalayanov, Genadiy; Sund, Christian; Winqvist, Anna; Pinho, Pedro; Maltseva, Tatiana; Morisson, Veronique; Leveque, Vincent; Rajyaguru, Sonal; Le Pogam, Sophie; Najera, Isabel; Benkestock, Kurt; Zhou, Xiao-Xiong; Maag, Hans; Cammack, Nick; Martin, Joseph A.; Swallow, Steven; Johansson, Nils Gunnar; Klumpp, Klaus; Smith, Mark

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 IC50 of 0.17 mu M in the genotype 1b subgenomic replicon system. The structure-activity relationships within this series of nucleoside analogues are discussed.

Published in

Journal of Medicinal Chemistry
2009, Volume: 52, number: 1, pages: 219-223

UKÄ Subject classification

Medicinal Chemistry

Publication identifier

DOI: https://doi.org/10.1021/jm800981y

Permanent link to this page (URI)

https://res.slu.se/id/publ/108045