Uncharged AZT and D4T derivatives of phosphonoformic and phosphonoacetic acids as anti-HIV pronucleosides

J Med Chem. 2004 Jul 1;47(14):3606-14. doi: 10.1021/jm0310176.

Abstract

Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives of AZT and d4T were synthesized and evaluated as anti-HIV agents. The efficacy of some of the synthesized compounds in cell cultures infected with HIV-1 was higher than that of the parent nucleosides and only slightly correlated to their stability in the phosphate buffer and human blood serum. The synthesized phosphonates are most probably prodrug forms of the corresponding nucleosides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Cell Line
  • Drug Stability
  • Foscarnet / analogs & derivatives*
  • Foscarnet / chemical synthesis
  • Foscarnet / pharmacology
  • HIV-1 / drug effects
  • Humans
  • Hydrolysis
  • Phosphonoacetic Acid / analogs & derivatives*
  • Phosphonoacetic Acid / chemical synthesis
  • Phosphonoacetic Acid / pharmacology
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology
  • Stavudine / analogs & derivatives*
  • Stavudine / chemical synthesis
  • Stavudine / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemical synthesis
  • Zidovudine / pharmacology

Substances

  • Anti-HIV Agents
  • Prodrugs
  • Foscarnet
  • Zidovudine
  • Stavudine
  • Phosphonoacetic Acid