Synthesis of N(1)-substituted analogues of (2R,4R)-4-amino-pyrrolidine-2,4-dicarboxylic acid as agonists, partial agonists, and antagonists of group II metabotropic glutamate receptors

Bioorg Med Chem Lett. 2001 Jul 23;11(14):1919-24. doi: 10.1016/s0960-894x(01)00329-8.

Abstract

The chemical synthesis of a series of N(1)-substituted derivatives of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid [(2R,4R)-APDC] as constrained analogues of gamma-substituted glutamic acids is described. Appropriate substitution of the N(1)-position results in agonist, partial agonist, or antagonist activity at mGluR2, mGluR3, and/or mGluR6.

MeSH terms

  • Animals
  • Binding Sites / physiology
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Glutamic Acid / metabolism
  • Inhibitory Concentration 50
  • Ligands
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / pharmacology*
  • Receptors, Glutamate / metabolism
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*

Substances

  • Ligands
  • Pyrrolidines
  • Receptors, Glutamate
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • metabotropic glutamate receptor 6
  • Glutamic Acid