Synthesis and anti-HIV activity of isonucleosides.
A series of isomeric 2',3'-dideoxynucleosides which contains a modified carbohydrate moiety has been prepared. This class of compounds was designed to mimic the activity of known anti-HIV dideoxynucleosides, while imparting enhanced chemical and enzymatic stability. Isonucleosides containing the standard heterocyclic bases (A, C, G, T) were synthesized via nucleophilic addition of the base to an isomeric sugar unit. Modified derivatives were generated by manipulation of the intact isonucleoside. Two of the compound prepared, iso-ddA (1) and iso-ddG (6), exhibit significant and selective anti-HIV activity, as well as beneficial hydrolytic stability.
Huryn
D M
DM
Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Sluboski
B C
BC
Tam
S Y
SY
Weigele
M
M
Sim
I
I
Anderson
B D
BD
Mitsuya
H
H
Broder
S
S
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D004355:Drug Stability; D015683:Gene Products, gag / Q000096:biosynthesis; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007536:Isomerism; D009000:Monocytes / Q000378:metabolism; D013057:Spectrum Analysis; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D015683:Gene Products, gag