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Author Notes:

Correspondence: Raymond F. Schinazi, Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, and Veterans Affairs Medical Center, 1670 Clairmont Road, Decatur, Georgia 30033, USA; Tel.: +1-404-728-7711; Fax: +1-404-417-1535; Email: rschina@emory.edu

Acknowledgments: We thank Emilie Fromentin, Aleksandr Obikhod, Sarah Solomon, and Jason Grier for excellent technical assistance.

Disclosures: Dr. Schinazi is a founder and major shareholder of RFS Pharma, LLC and his laboratory received no funding from RFS Pharma or vice versa.

All other authors have no competing interests.


Research Funding:

This work was supported in part by 2P30-AI-050409 (RFS), and the Department of Veterans Affairs (RFS), and by the Cancer Research Society (MG).

Dr. Götte received research grants from Tibotec, Merck, Gilead Sciences, AstraZeneca, Pfizer, and GlaxoSmithKline.


  • HCV
  • antiviral
  • 7-deazapurine
  • nucleoside
  • nucleotide
  • prodrug
  • Mitsunobu

Synthesis and antiviral activity of 2′-deoxy-2′-fluoro-2′-C-methyl-7-deazapurine nucleosides, their phosphoramidate prodrugs and 5′-triphosphates

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Journal Title:

Bioorganic and Medicinal Chemistry Letters


Volume 21, Number 23


, Pages 7094-7098

Type of Work:

Article | Post-print: After Peer Review


Thirty novel α- and β-D-2′-deoxy-2′-fluoro-2′-C-methyl-7-deazapurine nucleoside analogs were synthesized and evaluated for in vitro antiviral activity. Several α- and β-7-deazapurine nucleoside analogs exhibited modest anti-HCV activity and cytotoxicity. Four synthesized 7-deazapurine nucleoside phosphoramidate prodrugs (18–21) showed no anti-HCV activity, whereas the nucleoside triphosphates (22–24) demonstrated potent inhibitory effects against both wild-type and S282T mutant HCV polymerases. Cellular pharmacology studies in Huh-7 cells revealed that the 5′-triphosphates were not formed at significant levels from either the nucleoside or the phosphoramidate prodrugs, indicating that insufficient phosphorylation was responsible for the lack of anti-HCV activity. Evaluation of anti-HIV-1 activity revealed that an unusual α-form of 7-carbomethoxyvinyl substituted nucleoside (10) had good anti-HIV-1 activity (EC50 = 0.71 ± 0.25 μM; EC90 = 9.5 ± 3.3 μM) with no observed cytotoxicity up to 100 μM in four different cell lines.

Copyright information:

© 2011 Elsevier Ltd. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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