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

• Published in: Journal of medicinal chemistry 1981-08, Vol.24 (8), p.941-946
• Main Authors: Westover, James D, Revankar, Ganapathi R, Robins, Roland K, Madsen, Randall D, Ogden, John R, North, James A, Mancuso, Robert W, Rousseau, Robert J, Stephen, Edward L
• Format: Article
• Language: English
• Subjects: Antiviral Agents; DNA Viruses - drug effects; Drug Evaluation, Preclinical; Purine Nucleosides - pharmacology; RNA Viruses - drug effects; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00140a006

To examine the structural parameters necessary for antiviral efficacy of certain purine nucleosides, several 9-beta-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-beta-D-ribofuranosyl-6-iodopurine with cyanide ion. Certain 2-amino- and 2-methyl-9-beta-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-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 fever virus infected mice at 50 (mg/kg)/day gave a 55% survival rate on day 21 compared to a 30% survival in the controls.