(2S,1'S,2'R,3'R)-2-(2'-Carboxy-3'-hydroxymethylcyclopropyl) glycine is a highly potent group 2 and 3 metabotropic glutamate receptor agonist with oral activity

J Med Chem. 2004 Jan 15;47(2):456-66. doi: 10.1021/jm030967o.

Abstract

The asymmetric synthesis and biological activity of (2S,1'S,2'R,3'R)-2-(2'-carboxy-3'-hydroxymethylcyclopropyl) glycine ((+)-3) is described. This novel C-3' substituted carboxy cyclopropyl glycine is a highly potent group 2 and group 3 mGluR agonist that has proven to be orally active in both fear potentiated startle (animal model for anxiety) and PCP-induced motor activation (animal model for psychosis) assays in rats.

MeSH terms

  • Administration, Oral
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cyclic AMP / biosynthesis
  • Fear
  • Glycine / analogs & derivatives
  • Glycine / chemical synthesis*
  • Glycine / chemistry
  • Glycine / pharmacology
  • In Vitro Techniques
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / agonists*
  • Reflex, Startle / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 2-(2'-carboxy-3'-hydroxymethylcyclopropyl)glycine
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • Cyclic AMP
  • Glycine