Synthesis and Antiviral Activity of Certain 9-β-D-Ribofuranosylpurine-6-carboxamides

Article abstract of DOI:10.1021/jm00140a006

To examine the structural parameters necessary for antiviral efficacy of certain purine nucleosides, several 9-β-D-ribofuranosylpurine-6-carboxamides have been synthesized.Glycosylation of the Me3Si derivative of purine-6-carboxamide with protected ribofuranose in the presence of a Lewis acid gave the blocked nucleoside which on deprotection furnished 9-β-D-ribofuranosylpurine-6-carboxamide (6a).Alternatively, 6a was synthesized via the nucleophilic displacement of 9-β-D-ribofuranosyl-6-iodopurine with cyanide ion.Certain 2-amino- and 2-methyl-9-β-D-ribofuranosylpurine-6-carboxamides have also been prepared. 8-Carbamoylguanosine (16) has been prepared by homolytic acylation of the parent nucleoside.These compounds were tested against several RNA and DNA viruses in cell culture. 9-β-D-Ribofuranosylpurine-6-carboxamide (6a), the corresponding 6-thiocarboxamide (7b), and 4-amino-8-(β-D-ribofuranosylamino)pyrimido<5,4-d>pyrimidine (8) showed significant in vitro antiviral activity at nontoxic dosage levels. 6a employed in the treatment of Rift Valley fever virus infected mice at 50 (mg/kg)/day gave a 55percent survival rate on day 21 compared to a 30percent survival in the controls.