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Author Notes:

Corresponding author. Tel.: +34-985 105 013; fax: +34-985 103 448; mferrero@uniovi.es or vgs@uniovi.es or etheodor@ucsd.edu.

S.M.-M. thanks MEC for a predoctoral fellowship.

We also thank Dr. Y. Su (UCSD Mass Spectrometry) for mass analysis.

Subjects:

Research Funding:

Financial support of this work by the Spanish Ministerio de Educación y Ciencia (MEC) (Project MEC-CTQ-2007-61126) and PCTI (2006–2009)/FEDER (2007–2013) Asturias (Project EQUIP09-07) are gratefully acknowledged.

We also acknowledge the National Institutes of Health (NIH) for financial support of this work through Grant Number R01 GM081484.

We thank the National Science Foundation for instrumentation grants CHE9709183 and CHE0741968.

This work was also supported in part by NIH grant 2P30-AI-050409 and the Department of Veterans Affairs

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Physical Sciences
  • Biochemistry & Molecular Biology
  • Chemistry, Medicinal
  • Chemistry, Organic
  • Pharmacology & Pharmacy
  • Chemistry
  • Azanucleosides
  • Synthesis
  • Anti-HIV-1
  • Anti-HCV
  • L-Pyroglutamic acid
  • IMMUNODEFICIENCY-VIRUS TYPE-1
  • STEREOSELECTIVE-SYNTHESIS
  • OLIGONUCLEOTIDE SYNTHESIS
  • PYRROLIDINE SUGARS
  • HIV ACTIVITY
  • NUCLEOSIDES
  • DERIVATIVES
  • ANALOGS
  • CANCER
  • AZANUCLEOSIDES

Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides

Tools:

Journal Title:

Bioorganic and Medicinal Chemistry

Volume:

Volume 20, Number 23

Publisher:

, Pages 6885-6893

Type of Work:

Article | Post-print: After Peer Review

Abstract:

A series of 2′,3′-dideoxy-2′,2′-difluoro-4′- azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4′-azanucleosides were prepared as a separable mixture of α- and β-anomers. The 6-chloropurine analogue was obtained as a mixture of N 7 and N 9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4′-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC 50 = 36.9 μM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity.

Copyright information:

© 2012 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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