Synthesis and antiviral activity evaluation of novel 2-phenyl-4-(D-arabino-4'-cycloaminobutyl)triazoles: acyclonucleosides containing unnatural bases

Bioorg Med Chem. 2002 Apr;10(4):963-8. doi: 10.1016/s0968-0896(01)00349-2.

Abstract

Five 2-phenyl-4-(D-arabino-4'-cycloamino-3'-hydroxy-O-1',2'-isopropylidene-butyl)-2H-1,2,3-triazoles, acyclonucleosides containing unnatural bases have been synthesised by opening of the epoxide ring of 2-phenyl-4-(D-arabino-3',4'-epoxy-O-1',2'-isopropylidenebutyl)-2H-1,2,3-triazole with the corresponding cyclic amines in 70-85% yields. The starting arabino-epoxytriazole was prepared in five steps starting from D-glucose in an overall yield of 15%. All the five triazolylacyclonucleosides were unambiguously identified on the basis of their spectral data. The structure of one of the intermediates, that is 2-phenyl-4-(D-arabino-1',2',3',4'-tetrahydroxybutyl)-2H-1,2,3-triazole was confirmed by its X-ray crystallographic studies. These acyclonucleosides were subjected to antiviral activity evaluation in CEM-SS cell-based anti HIV assay with the lymphocytropic virus strains HIV-1(IIIB) and HIV-1(RF).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Arabinose / chemical synthesis*
  • Arabinose / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • HIV-1 / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology

Substances

  • Anti-HIV Agents
  • Antiviral Agents
  • Triazoles
  • Arabinose