Antiviral activity of C-alkylated purine nucleosides obtained by cross-coupling with tetraalkyltin reagents.
2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides. The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure. The 6-alkylated-9-beta-D-ribofuranosylpurines as well as 2-ethyladenosine were cytotoxic at relatively low concentrations (0.8-10 micrograms/mL). 8-Methyladenosine was a potent and selective inhibitor of vaccinia virus, whereas 8-ethyl- and 8-vinyladenosine were specifically inhibitory to respiratory syncytial virus. 8-Vinyladenosine displayed particular activity against herpes simplex virus (type 1).
Van Aerschot
A A
AA
Department of Medinical Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Mamos
P
P
Weyns
N J
NJ
Ikeda
S
S
De Clercq
E
E
Herdewijn
P A
PA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D009947:Organotin Compounds; D012136:Respiratory Syncytial Viruses / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects
D000998:Antiviral Agents; D007202:Indicators and Reagents; D009947:Organotin Compounds; C083597:8-vinyladenosine; C070330:8-methyladenosine; C083596:8-ethyladenosine; D000241:Adenosine