Development and optimization of anti-HIV nucleoside analogs and prodrugs: A review of their cellular pharmacology, structure-activity relationships and pharmacokinetics
Xl. Tan et al., Development and optimization of anti-HIV nucleoside analogs and prodrugs: A review of their cellular pharmacology, structure-activity relationships and pharmacokinetics, ADV DRUG DE, 39(1-3), 1999, pp. 117-151
Significant improvements in antiviral therapy have been realized over the p
ast 10 years. Numerous nucleoside analogs, as well as prodrugs of active co
mpounds, have been synthesized and tested for anti-HIV activity. In additio
n to the five nucleoside analogs currently used clinically for the treatmen
t of HIV infection, a broad spectrum of anti-HIV nucleoside analogs (includ
ing 2',3'-dideoxynucleoside analogs, oxathiolanyl 2',3'-dideoxynucleoside a
nalogs, dioxolanyl 2',3'-dideoxynucleoside analogs, carbocyclic 2',3'-dideo
xynucleoside analogs and acyclic nucleoside analogs) and their prodrugs (in
cluding eater prodrugs, phospholipid prodrugs, dihydropyridine prodrugs, pr
onucleotides and dinucleotide analogs), targeted at HIV reverse transcripta
se, are reviewed with focus on structure-activity relationships, cellular p
harmacology and pharmacokinetics. Several of these anti-viral agents show p
romise in the treatment of AIDS. (C) 1999 Elsevier Science B.V. All rights
reserved.