Design, synthesis, and biological evaluation of new 2¡ä-deoxy-2¡ä-fluoro-4¡ä-triazole cytidine nucleosides as potent antiviral agents

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• 作者：Jie Wu ; Wenquan Yu ; Leixia Fu ; Wu He ; Yao Wang ; Baoshan Chai ; Chuanjun Song ; ^{chjsong@zzu.edu.cn} ; Junbiao Chang ; ^{changjunbiao@zzu.edu.cn}
• 关键词：2&prime ; -Deoxy-2&prime ; -fluoro-4&prime ; -triazole nucleosides ; Anti-HIV activity ; Nucleoside reverse transcriptase inhibitor (NRTI) ; Anti-HBV activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：63
• 期：Complete
• 页码：739-745
• 全文大小：533 K

文摘

A series of 4¡ä-[1,2,3]triazole-2¡ä-deoxy-2¡ä-fluoro-¦Â-d-arabinofuranosylcytosines (9-17) were prepared by Cu(I)-mediated [3?+?2] cycloaddition reactions (CuAAC) of 1-(4¡ä-azido-2¡ä-deoxy-2¡ä-fluoro-¦Â-d-arabinofuranosyl)cytosine (1) with appropriate alkynes in good yields. Their structures were fully established by ¹H NMR, ¹³C NMR, HRMS, and elemental analysis. Most of these nucleoside analogs exhibited potent anti-HIV-1 activity with no cytotoxicity observed at the highest tested concentration up to 25?¦ÌM. Among them, compounds 9, 10 and 13 exhibited extremely potent antiviral activity, thus had a great potential for further development as novel nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV-1 infection. Besides, the anti-HBV activity of compounds 10, 11 and 17 had been investigated.