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

Abstract

A series of 4'-[1,2,3]triazole-2'-deoxy-2'-fluoro-β-d-arabinofuranosylcytosines (9-17) were prepared by Cu(I)-mediated [3 + 2] cycloaddition reactions (CuAAC) of 1-(4'-azido-2'-deoxy-2'-fluoro-β-d-arabinofuranosyl)cytosine (1) with appropriate alkynes in good yields. Their structures were fully established by (1)H NMR, (13)C 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 μM. 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.

• Authors: Jie Wu, Wenquan Yu, Leixia Fu, Wu He, Yao Wang, Baoshan Chai, Chuanjun Song, Junbiao Chang
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 63 Pg. 739-45 (May 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23570720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antiviral Agents
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Triazoles
• Cytidine

Topics

• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Cell Survival (drug effects)
• Cytidine (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Design
• Enzyme-Linked Immunosorbent Assay
• HEK293 Cells
• HIV-1 (drug effects)
• Hep G2 Cells
• Hepatitis B Surface Antigens (metabolism)
• Hepatitis B e Antigens (metabolism)
• Hepatitis B virus (drug effects, metabolism)
• Humans
• Models, Chemical
• Molecular Structure
• Triazoles (chemical synthesis, chemistry, pharmacology)