2. Academic Validation
  3. Fluorinated sugar analogues of potential anti-HIV-1 nucleosides

Fluorinated sugar analogues of potential anti-HIV-1 nucleosides

  • J Med Chem. 1991 May;34(5):1640-6. doi: 10.1021/jm00109a017.
J T Huang 1,  L C Chen,  L B Wang,  M H Kim,  J A Warshaw,  D Armstrong,  Q Y Zhu,  T C Chou,  K A Watanabe,  J Matulic-Adamic
Affiliations

Affiliation

  • 1 Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division of Graduate School of Medical Sciences, Cornell University, New York, New York 10021.
PMID: 2033590 DOI: 10.1021/jm00109a017
Abstract

In order to obtain agents with therapeutic indices superior to those of AZT, FLT, or D4T, several analogues of anti-HIV-1 nucleosides were synthesized. These include 2',3'-dideoxy-2',3' -difluoro-5-methyluridine (13), its arabino analogue 19, arabino-5-methylcytosine analogue 21, 3'-deoxy-2',3'-didehydro-2' -fluorothymidine (25), 3'-azido-2',3'-dideoxy-2'-fluoro-5-methyluridine (29), 2'-azido-3'-fluoro-2',3'-dideoxy-5-methyluridine (31), and 2'3'-dideoxy-2' -fluoro-5-methyluridine (37). These new nucleosides were screened for their activity against HIV and feline TLV in vitro. None of the compounds showed significant activity. It is interesting to note that such a small modification in the sugar moiety of active anti-HIV nucleosides (i.e., displacement of hydrogen by fluorine) almost completely inactivate the agents.

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