Synthesis and antiviral evaluation of cyclopentyl nucleoside phosphonates

Eur J Med Chem. 2018 Apr 25:150:616-625. doi: 10.1016/j.ejmech.2018.03.008. Epub 2018 Mar 10.

Abstract

The synthesis of both 2'-hydroxy-3'-deoxy and 2'-deoxy-3'-hydroxy cyclopentyl nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine and guanine from a single precursor has been performed. The guanine containing analogues showed antiviral activity. Especially the 3'-deoxy congener 23 was active, displaying an EC50 of 5.35 μM against TK+ VZV strain and an EC50 of 8.83 μM against TK- VZV strain, besides lacking cytotoxicity. However, the application of phosphonodiamidate prodrug strategy did not lead to a boost in antiviral activity.

Keywords: Antiviral; Carbocyclic nucleoside; Nucleoside phosphonate; Prodrug.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cyclopentanes / chemical synthesis
  • Cyclopentanes / chemistry
  • Cyclopentanes / pharmacology*
  • DNA Viruses / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nucleosides / chemical synthesis
  • Nucleosides / chemistry
  • Nucleosides / pharmacology*
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Cyclopentanes
  • Nucleosides
  • Organophosphonates