Synthesis, cytostatic and anti-HCV activity of 6-(N-substituted aminomethyl)-, 6-(O-substituted hydroxymethyl)- and 6-(S-substituted sulfanylmethyl)purine nucleosides

Bioorg Med Chem. 2008 Mar 1;16(5):2329-66. doi: 10.1016/j.bmc.2007.11.067. Epub 2007 Nov 29.

Abstract

An efficient and facile synthesis of a large series of diverse 6-(N-substituted aminomethyl)-, 6-(O-substituted hydroxymethyl)- and 6-(S-substituted sulfanylmethyl)purine nucleosides (55 examples of both ribo- and 2'-deoxyribonucleosides), aimed at identifying novel homologues of natural nucleosides, was developed. The key transformation involved nucleophilic substitutions of Tol-protected 6-(mesyloxymethyl)purine nucleosides by primary or secondary amines, alcoholates or thiolates. While the 2'-deoxyribonucleosides were inactive, the ribonucleosides exerted considerable cytostatic effects and some anti-HCV activity with low selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Cytostatic Agents / chemical synthesis*
  • Cytostatic Agents / chemistry
  • Cytostatic Agents / pharmacology*
  • Hepacivirus / drug effects*
  • Humans
  • Hydroxylation
  • Mesylates / chemistry
  • Methylation
  • Mice
  • Molecular Structure
  • Purine Nucleosides / chemical synthesis*
  • Purine Nucleosides / chemistry
  • Purine Nucleosides / pharmacology*
  • Structure-Activity Relationship
  • Sulfur Compounds / chemical synthesis
  • Sulfur Compounds / chemistry
  • Sulfur Compounds / pharmacology

Substances

  • Antiviral Agents
  • Cytostatic Agents
  • Mesylates
  • Purine Nucleosides
  • Sulfur Compounds