Synthesis and antiviral activities of hexadecyloxypropyl prodrugs of acyclic nucleoside phosphonates containing guanine or hypoxanthine and a (S)-HPMP or PEE acyclic moiety

Eur J Med Chem. 2012 Sep:55:307-14. doi: 10.1016/j.ejmech.2012.07.027. Epub 2012 Jul 24.

Abstract

Hexadecyloxypropyl esters of acyclic nucleoside phosphonates containing guanine (G) or hypoxanthine (Hx) and a (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] [(S)-HPMP] or 2-(2-phosphonoethoxy)ethyl (PEE) acyclic moiety have been prepared. The activity of the prodrugs was evaluated in vitro against different virus families. Whereas ester derivatives of PEEHx and (S)-HPMPHx were antivirally inactive, monoesters of PEEG, and mono- and diesters of (S)-HPMPG showed pronounced antiviral activity against vaccinia virus and/or herpesviruses. Monoesters of (S)-HPMPG emerged as the most potent and selective derivatives against these DNA viruses. None of the compounds were inhibitory against RNA viruses and retroviruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • Cell Line
  • Chemistry Techniques, Synthetic
  • DNA Viruses / drug effects
  • Guanine / analogs & derivatives*
  • Guanine / chemistry*
  • Humans
  • Hypoxanthine / chemistry*
  • Hypoxanthines / chemistry*
  • Nucleosides / chemistry*
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / chemistry
  • Organophosphonates / metabolism
  • Organophosphonates / pharmacology*
  • Phosphorous Acids / chemistry*
  • Prodrugs / metabolism*
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Hypoxanthines
  • Nucleosides
  • Organophosphonates
  • Phosphorous Acids
  • Prodrugs
  • Hypoxanthine
  • Guanine