(2R,1'S,2'R,3'S)-2-(2'-Carboxy-3'-phenylcyclopropyl)glycine (PCCG-13), the first potent and selective competitive antagonist of phospholipase D-coupled metabotropic glutamate receptors: asymmetric synthesis and preliminary biological properties

J Med Chem. 1999 Jul 15;42(14):2716-20. doi: 10.1021/jm990128v.

Abstract

The asymmetric synthesis of (2R,1'S,2'R, 3'S)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-13), a trisubstituted carboxycyclopropylglycine endowed with unusual stereochemical features, is described. Preliminary biological evaluation demonstrates PCCG-13 as a very potent and selective competitive antagonist for the novel class of metabotropic glutamate (mGlu) receptors coupled to the activity of phospholipase D (PLD). PCCG-13 is therefore a useful tool for the exploration of the physiopathological role of this novel class of receptors.

MeSH terms

  • Animals
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology
  • Glycerophospholipids / biosynthesis
  • Glycine / analogs & derivatives*
  • Glycine / chemical synthesis
  • Glycine / chemistry
  • Glycine / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Phospholipase D / metabolism*
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / metabolism
  • Stereoisomerism
  • Type C Phospholipases / metabolism

Substances

  • 2-(2'-carboxy-3'-phenylcyclopropyl)glycine
  • Cyclopropanes
  • Glycerophospholipids
  • Receptors, Metabotropic Glutamate
  • phosphatidylethanol
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Type C Phospholipases
  • Phospholipase D
  • Glycine