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Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents.

Publication ,  Journal Article
Wang, Q; Hu, W; Wang, S; Pan, Z; Tao, L; Guo, X; Qian, K; Chen, C-H; Lee, K-H; Chang, J
Published in: Eur J Med Chem
September 2011

We prepared 1-(4'-azido-2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)cytosine (10) and its hydrochloride salt (11) as potential antiviral agents based on the favorable antiviral profiles of 4'-substituted nucleosides. Compounds 10 and 11 were synthesized from 1,3,5-O-tribenzoyl-2-deoxy-2-fluoro-D-arabinofuranoside in multiple steps, and their structures were unequivocally established by IR, (1)H NMR, (13)C NMR, and (19)F NMR spectroscopy, HRMS, and X-ray crystallography. Compounds 10 and 11 exhibited potent anti-HIV-1 activity (EC(50): 0.3 and 0.13 nM, respectively) without significant cytotoxicity in concentrations up to 100 μM. Compound 11 exhibited extremely potent anti-HIV activity against NL4-3 (wild-type), NL4-3 (K101E), and RTMDR viral strains, with EC(50) values of 0.086, 0.15, and 0.11 nM, respectively. Due to the high potency of 11, it was also screened against an NIH Reagent Program NRTI-resistant virus panel containing eleven mutated viral strains and for cytotoxicity against six different human cell lines. The results of this screening indicated that 11 is a novel NRTI that could be developed as an anti-AIDS clinical trial candidate to overcome drug-resistance issues.

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Published In

Eur J Med Chem

DOI

EISSN

1768-3254

Publication Date

September 2011

Volume

46

Issue

9

Start / End Page

4178 / 4183

Location

France

Related Subject Headings

  • Spectrophotometry, Infrared
  • Nucleosides
  • Models, Molecular
  • Medicinal & Biomolecular Chemistry
  • Mass Spectrometry
  • Magnetic Resonance Spectroscopy
  • Inhibitory Concentration 50
  • Humans
  • Cytarabine
  • Crystallography, X-Ray
 

Citation

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Wang, Q., Hu, W., Wang, S., Pan, Z., Tao, L., Guo, X., … Chang, J. (2011). Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. Eur J Med Chem, 46(9), 4178–4183. https://doi.org/10.1016/j.ejmech.2011.06.020
Wang, Qiang, Weidong Hu, Shuyang Wang, Zhenliang Pan, Le Tao, Xiaohe Guo, Keduo Qian, Chin-Ho Chen, Kuo-Hsiung Lee, and Junbiao Chang. “Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents.Eur J Med Chem 46, no. 9 (September 2011): 4178–83. https://doi.org/10.1016/j.ejmech.2011.06.020.
Wang Q, Hu W, Wang S, Pan Z, Tao L, Guo X, et al. Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. Eur J Med Chem. 2011 Sep;46(9):4178–83.
Wang, Qiang, et al. “Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents.Eur J Med Chem, vol. 46, no. 9, Sept. 2011, pp. 4178–83. Pubmed, doi:10.1016/j.ejmech.2011.06.020.
Wang Q, Hu W, Wang S, Pan Z, Tao L, Guo X, Qian K, Chen C-H, Lee K-H, Chang J. Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. Eur J Med Chem. 2011 Sep;46(9):4178–4183.
Journal cover image

Published In

Eur J Med Chem

DOI

EISSN

1768-3254

Publication Date

September 2011

Volume

46

Issue

9

Start / End Page

4178 / 4183

Location

France

Related Subject Headings

  • Spectrophotometry, Infrared
  • Nucleosides
  • Models, Molecular
  • Medicinal & Biomolecular Chemistry
  • Mass Spectrometry
  • Magnetic Resonance Spectroscopy
  • Inhibitory Concentration 50
  • Humans
  • Cytarabine
  • Crystallography, X-Ray