Synthesis and determination of antiviral activity of the 2'(3')-O-methyl derivatives of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide).
Diazomethane treatment of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) in the presence of SnCl2 as catalyst led to quantitative formation of the 2'-O-methyl and 3'-O-methyl derivatives of the parent compound. The products were successfully fractionated on a basic ion-exchange column and isolated in crystalline form. Indentification was based on the elution sequence from the column and on 1H NMR spectroscopy. Both derivatives were found to be inactive, relative to the parent compound, against several virus types in cell culture. Unlike ribavirin itself, the 2'(3')-O-methyl derivatives did not suppress cellular DNA synthesis. NMR data showed that the loss of biologic activity upon 2'(3')-O-methylation was not due to a change of conformation of the nucleoside sugar moiety.
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D011817:Rabbits; D012254:Ribavirin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D012263:Ribonucleosides / Q000138:chemical synthesis*
D000998:Antiviral Agents; D012263:Ribonucleosides; D012254:Ribavirin