Synthesis and Antiviral Activity of 5-Substituted Cytidine Analogues: Identification of a Potent Inhibitor of Viral RNA-Dependent RNA Polymerases
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- 作者：Daniel A. Harki ; Jason D. Graci ; Jessica E. Galarraga ; William J. Chain ; Craig E. Cameron ; Blake R. Peterson
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：October 19, 2006
- 年：2006
- 卷：49
- 期：21
- 页码：6166 - 6169
- 全文大小：194K
- 年卷期：v.49,no.21(October 19, 2006)
- ISSN：1520-4804
文摘
As part of our studies of lethal viral mutagens, a series of5-substituted cytidine analogues were synthesized and evaluated forantiviral activity. Among the compounds examined, 5-nitrocytidine waseffective against poliovirus (PV) and coxsackievirus B3 (CVB3) andexhibited greater activity than the clinically employed drug ribavirin.Instead of promoting viral mutagenesis, 5-nitrocytidine triphosphateinhibited PV RNA-dependent RNA polymerase (Kd = 1.1 ± 0.1 
M),and this inhibition is sufficient to explain the observed antiviral activity.
M),and this inhibition is sufficient to explain the observed antiviral activity.