Synthesis and antiviral activity evaluation of 3'-fluoro-3'-deoxyribonucleosides: broad-spectrum antiviral activity of 3'-fluoro-3'-deoxyadenosine.
Five 3'-fluorinated ribonucleosides were prepared and evaluated for their inhibitory properties against different viruses. The synthesis of these compounds was achieved by treatment of 2',5'-di-O-tritylated nucleoside analogues possessing a xylo-configuration with diethylaminosulfur trifluoride, followed by deprotection. 3'-Fluoro-3'-deoxyadenosine was active against a broad range of viruses, encompassing both DNA viruses [pox (vaccinia)], single-stranded (+) RNA viruses [picorna (polio, Coxsackie B), toga (sindbis, Semliki Forest)] and double-stranded RNA viruses (reo). In its antiviral activity spectrum 3'-fluoro-3'-deoxyadenosine clearly differed from those adenosine analogues that are known as inhibitors of S-adenosylhomocysteine hydrolase. 3'-Fluoro-3'-deoxyadenosine also proved effective in vivo, in inhibiting tail lesion formation in mice inoculated intravenously with vaccinia virus.
Van Aerschot
A
A
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Herdewijn
P
P
Janssen
G
G
Cools
M
M
De Clercq
E
E
D043383:Adenosylhomocysteinase; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004267:DNA Viruses / Q000187:drug effects; D003839:Deoxyadenosines / Q000008:administration & dosage / Q000494:pharmacology; D003854:Deoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006867:Hydrolases; D051379:Mice; D012328:RNA Viruses / Q000187:drug effects; D011817:Rabbits; D014615:Vaccinia / Q000188:drug therapy
D000998:Antiviral Agents; D003839:Deoxyadenosines; D003854:Deoxyribonucleotides; C062976:3'-fluoro-3'-deoxyadenosine; D006867:Hydrolases; D043383:Adenosylhomocysteinase