Synthesis and antiviral activity of certain 9-.beta.-D-ribofuranosylpurine-6-carboxamides

Abstract

To examine the structural parameters necessary for antiviral efficacy of certain purine nucleosides, several 9-.beta.-D-ribofuranosylpurine-6-carboxamides were 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-.beta.-D-ribofuranosylpurine-6-carboxamide (6a). Alternatively, 6a was synthesized via the nucleophilic displacement of 9-.beta.-D-ribofuranosyl-6-iodopurine with cyanide ion. Certain 2-amino- and 2-methyl-9-.beta.-D-ribofuranosylpurine-6-carboxyamides were also prepared. 8-Carbamoylguanosine (16) was prepared by homolytic acylation of the parent nucleoside. These compounds were tested against several RNA and DNA viruses in cell culture. 9-.beta.-D-Ribofuranosylpurine-6-carboxamide (6a), the corresponding 6-thiocarboxamide (7b) and 4-amino-8-(.beta.-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 fewer virus infected mice at 50 (mg/kg) per day gave a 55% survival rate on day 21 compared to a 30% survival in the controls.