Synthesis and antiviral activity of novel acyclic nucleoside analogues of 5-(1-azido-2-haloethyl)uracils

被引：28

作者：

Kumar, R ^{[1
]}

Sharma, N ^{[1
]}

Nath, M ^{[1
]}

Saffran, HA ^{[1
]}

Tyrrell, DLJ ^{[1
]}

机构：

[1] Univ Alberta, Fac Med, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2H7, Canada

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 24期

关键词：

D O I：

10.1021/jm010227k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We present the discovery of a novel category of 5-substituted acyclic pyrimidine nucleosides as potent antiviral agents. A series of 1-[(2-hydroxyethoxy)methyl] (5-7), 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl] (8-10), and 1-[4-hydroxy-3-(hydroxymethyl)-1-butyl] (11-13) derivatives of 5-(1-azido-2-haloethyl)uracil were synthesized and evaluated for their biological activity in cell culture. 1-[4-Hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azido-2-chloroethyl)uracil (12) was the most effective antiviral agent in the in vitro assays against DHBV (EC50 = 0.31-1.55 muM) and HCMV (EC50 = 3.1 muM). None of the compounds investigated showed any detectable toxicity to several stationary and proliferating host cells.

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页码：4225 / 4229

页数：5

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