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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Wang, Q; Hu, W; Wang, S; Pan, Z; Tao, L; Guo, X; Qian, K; Chen, C-H; Lee, K-H; Chang, J

Published Date

  • September 2011

Published In

Volume / Issue

  • 46 / 9

Start / End Page

  • 4178 - 4183

PubMed ID

  • 21745701

Pubmed Central ID

  • PMC3164908

Electronic International Standard Serial Number (EISSN)

  • 1768-3254

Digital Object Identifier (DOI)

  • 10.1016/j.ejmech.2011.06.020


  • eng

Conference Location

  • France