Document 0914
 DOCN  M9540914
 TI    Synthesis, hydrolytic behavior, and anti-HIV activity of selected
       acyloxyalkyl esters of trisodium phosphonoformate (foscarnet sodium).
 DT    9504
 AU    Iyer RP; Boal JH; Phillips LR; Thakker DR; Egan W; Center for Biologics
       Evaluation and Research, Food and Drug; Administration, Bethesda,
       Maryland 20892.
 SO    J Pharm Sci. 1994 Sep;83(9):1269-73. Unique Identifier : AIDSLINE
       MED/95131381
 AB    The synthesis and anti-HIV activity of selected (acyloxy)alkyl esters of
       trisodium phosphonoformate (foscarnet sodium) are described. The
       conversion of bis(trimethylsilyl) (alkoxycarbonyl)phosphonates 11a-d to
       the corresponding disilver salts 12a-d and their subsequent reaction
       with iodoalkyl acrylates 4a-c gave the desired bis(acyloxyalkyl)
       phosphonates 6-9(a-c). Of the analogs tested, only the dichlorophenyl
       analog 9a showed a dose-dependent inhibition of HIV activity in H9
       cells. Using 31P-NMR, bioreversibility has been investigated in an
       attempt to rationalize these results.
 DE    Antiviral Agents/*CHEMICAL SYNTHESIS/*PHARMACOLOGY  Cell Line
       Cytopathogenic Effect, Viral/DRUG EFFECTS  Foscarnet/*ANALOGS &
       DERIVATIVES/CHEMICAL SYNTHESIS/*PHARMACOLOGY  Human  Hydrolysis
       HIV-1/*DRUG EFFECTS/ENZYMOLOGY  Nuclear Magnetic Resonance
       Prodrugs/*CHEMICAL SYNTHESIS/*PHARMACOLOGY  Reverse
       Transcriptase/ANTAGONISTS & INHIB  Support, U.S. Gov't, P.H.S.  JOURNAL
       ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).