Synthesis and antiviral acticity of some phosphates of the broad-spectrum antiviral nucleoside, 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin).
1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide 5'-phosphate (2) was prepared and converted into the following derivatives: the 5'-phosphoramidate 3, the 5'-diphosphate 4, the 5'-triphosphate 5, and the cyclic 3',5'-phosphate 6. The cyclic 2',3'-phosphate 7 was prepared from the parent nucleoside, 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (1), and was opened to the 2'(3')-phosphate 8. These compounds were found to exhibit significant antiviral activity against several viruses in cell culture. Ribavirin 5'-phosphate (2) was shown to be effective when tested against lethal infections in mice caused by influenza A2, influenza B, and murine hepatitis viruses.
D000256:Adenoviridae / Q000187:drug effects; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects; D012229:Rhinovirus / Q000187:drug effects; D012254:Ribavirin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D012263:Ribonucleosides / Q000138:chemical synthesis*; D012265:Ribonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D018139:Simplexvirus / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects
D000998:Antiviral Agents; D012263:Ribonucleosides; D012265:Ribonucleotides; D012254:Ribavirin