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

J Med Chem. 1981 Aug;24(8):941-6. doi: 10.1021/jm00140a006.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents*
  • DNA Viruses / drug effects
  • Drug Evaluation, Preclinical
  • Purine Nucleosides / pharmacology*
  • RNA Viruses / drug effects
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Purine Nucleosides