| Literature DB >> 19341305 |
David B Smith1, Genadiy Kalayanov, Christian Sund, Anna Winqvist, Tatiana Maltseva, Vincent J-P Leveque, Sonal Rajyaguru, Sophie Le Pogam, Isabel Najera, Kurt Benkestock, Xiao-Xiong Zhou, Ann C Kaiser, Hans Maag, Nick Cammack, Joseph A Martin, Steven Swallow, Nils Gunnar Johansson, Klaus Klumpp, Mark Smith.
Abstract
The discovery of 4'-azidocytidine (3) (R1479) (J. Biol. Chem. 2006, 281, 3793; Bioorg. Med. Chem. Lett. 2007, 17, 2570) as a potent inhibitor of RNA synthesis by NS5B (EC(50) = 1.28 microM), the RNA polymerase encoded by hepatitis C virus (HCV), has led to the synthesis and biological evaluation of several monofluoro and difluoro derivatives of 4'-azidocytidine. The most potent compounds in this series were 4'-azido-2'-deoxy-2',2'-difluorocytidine and 4'-azido-2'-deoxy-2'-fluoroarabinocytidine with antiviral EC(50) of 66 nM and 24 nM in the HCV replicon system, respectively. The structure-activity relationships within this series were discussed, which led to the discovery of these novel nucleoside analogues with the most potent compound, showing more than a 50-fold increase in antiviral potency as compared to 4'-azidocytidine (3).Entities:
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Year: 2009 PMID： 19341305 DOI： 10.1021/jm801595c
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446