Document 0293
 DOCN  M94A0293
 TI    Certain phosphoramidate derivatives of dideoxy uridine (ddU) are active
       against HIV and successfully by-pass thymidine kinase.
 DT    9412
 AU    McGuigan C; Bellevergue P; Sheeka H; Mahmood N; Hay AJ; Welsh School of
       Pharmacy, University of Wales Cardiff, UK.
 SO    FEBS Lett. 1994 Aug 29;351(1):11-4. Unique Identifier : AIDSLINE
       MED/94357262
 AB    As part of our effort to deliver masked phosphates inside living cells
       we have discovered that certain phosphate triester derivatives of the
       inactive nucleoside analogue, dideoxy uridine (ddU) are inhibitors of
       HIV replication at microM levels. Moreover, we note that certain
       phosphoramidate derivatives retain their activity in thymidine
       kinase-deficient cells, which indicates that they do indeed act by
       intracellular release of the free nucleotide, and that they successfully
       by-pass the nucleoside kinase. The increased structural freedom in drug
       design which this allows may have implications for dealing with the
       emergence of resistance and may stimulate the discovery of improved
       therapeutic agents.
 DE    Antiviral Agents/*PHARMACOLOGY  Cell Line  Cell Line, Transformed
       Chromatography, High Pressure Liquid
       Dideoxynucleosides/CHEMISTRY/*PHARMACOLOGY  Human  HIV-1/*DRUG
       EFFECTS/PHYSIOLOGY  Molecular Structure  Nuclear Magnetic Resonance
       Organophosphorus Compounds/*CHEMISTRY  Spectrum Analysis, Mass  Support,
       Non-U.S. Gov't  Thymidine Kinase/*DRUG EFFECTS  *Uridine  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).