Design of new mononucleotide prodrugs: aryl (SATE) phosphotriester derivatives

Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):315-21. doi: 10.1081/NCN-100002302.

Abstract

Synthesis, biological activities and decomposition kinetics of novel phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-tButyl-2-thioethyl (tBuSATE) group and L-tyrosinyl residues are reported. All the derivatives appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments. The proposed decomposition process of these mixed phosphotriesters may involve successively an esterase and then a phosphodiesterase activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cells, Cultured
  • Drug Design
  • Drug Stability
  • Esters / chemical synthesis
  • Esters / chemistry
  • Esters / pharmacology
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Virus Replication / drug effects
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemical synthesis
  • Zidovudine / pharmacology

Substances

  • Anti-HIV Agents
  • Esters
  • Prodrugs
  • Zidovudine