Synthesis and antiviral activity of cyclopropyl-spirocarbocyclic adenosine, (4R,5S,6R,7R)-4-(6-amino-9H-purin-9-yl)-7-(hydroxymethyl)spiro[2.4]heptane-5,6-diol against hepatitis C virus

Bioorg Med Chem Lett. 2011 Jul 1;21(13):3982-5. doi: 10.1016/j.bmcl.2011.05.012. Epub 2011 May 11.

Abstract

An efficient method was developed for the synthesis of 6-exocyclic methylene carbocyclic intermediate 4. The Simmons-Smith cyclopropanation protocol was applied on the 6-exocyclic methylene of intermediate 4 and demonstrated its utility for the synthesis of novel class of a spiro-carbocyclic nucleoside analog 8. The titled compound 8 demonstrated a significant antiviral activity against HCV with EC(50) values of 0.273 and 0.368 μM in genotypes 1A and 1B, respectively.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • Crystallography, X-Ray
  • Hepacivirus / drug effects*
  • Heptanes / chemical synthesis*
  • Heptanes / chemistry
  • Heptanes / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • 4-(6-amino-9H-purin-9-yl)-7-(hydroxymethyl)spiro(2.4)heptane-5,6-diol
  • Antiviral Agents
  • Heptanes
  • Spiro Compounds
  • Adenosine