Potent new leucine aminopeptidase inhibitor of novel structure synthesised by a modified Wadsworth-Emmons (Horner) Wittig procedure

Bioorg Med Chem Lett. 2000 Jul 3;10(13):1481-2. doi: 10.1016/s0960-894x(00)00261-4.

Abstract

The use of a leucine-derived alpha-keto-beta-aldehyde (glyoxal) as a substrate in the Horner-Emmons (Wadsworth) Wittig reaction has enabled the synthesis of (Z)-7-methyl-5(S)-amino-4-oxo-methyl-oct-2-eneoate. This novel compound is a potent inhibitor (Ki = 76 nM) of leucine aminopeptidase and provides an interesting new template for the development of metallopeptidase inhibitors.

MeSH terms

  • Chemistry, Organic / methods
  • Glyoxal / chemistry*
  • Leucyl Aminopeptidase / antagonists & inhibitors*
  • Magnetic Resonance Spectroscopy
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology

Substances

  • Protease Inhibitors
  • Glyoxal
  • Leucyl Aminopeptidase