Development and optimization of anti-HIV nucleoside analogs and prodrugs: A review of their cellular pharmacology, structure-activity relationships and pharmacokinetics

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.