Synthesis and in vitro evaluation of a phosphonate prodrug: bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine

Antiviral Res. 1992 Sep;19(3):267-73. doi: 10.1016/0166-3542(92)90084-i.

Abstract

9-(2-Phosphonylmethoxyethyl)adenine (PMEA; 1) was acylated with chloromethyl pivalate to afford bis(pivaloyloxymethyl) PMEA (2). The ester prodrug demonstrated enhanced in vitro potency against HSV-2 greater than 150-fold higher than the parent compound. The antiviral activity of 2 was 50-fold better than PMEA against HSV-1, and equipotent against HIV and HCMV. The toxicity of 2 was studied in both resting and growing cells.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemical synthesis
  • Adenine / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cytomegalovirus / drug effects
  • Drug Evaluation, Preclinical
  • HIV / drug effects
  • Humans
  • Organophosphonates*
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology*
  • Simplexvirus / drug effects

Substances

  • Antiviral Agents
  • Organophosphonates
  • Prodrugs
  • adefovir
  • Adenine