Lactate cannot substitute for alanine in d4T-based anti-HIV nucleotide prodrugs--despite efficient esterase-mediated hydrolysis

Bioorg Med Chem Lett. 1998 Nov 3;8(21):2949-54. doi: 10.1016/S0960-894X(98)00530-7.

Abstract

As part of our on-going effort to deliver masked phosphates of antiviral nucleosides inside living cells we have previously discovered that amino acid-derived phosphoramidates are particularly effective. Here we report that lactate analogues, with a simple change of bridging nitrogen for oxygen, are virtually inactive as antiviral agents and apparently do not achieve intracellular nucleoside phosphate delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine
  • Anti-HIV Agents / pharmacology*
  • Esterases / pharmacology*
  • Hydrolysis
  • Lactic Acid
  • Nucleotides / pharmacology*
  • Prodrugs / metabolism
  • Prodrugs / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Nucleotides
  • Prodrugs
  • Lactic Acid
  • Esterases
  • Alanine