Synthesis and metabotropic glutamate receptor antagonist activity of N1-substituted analogs of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylic acid

Bioorg Med Chem Lett. 1998 Aug 4;8(15):1985-90. doi: 10.1016/s0960-894x(98)00352-7.


A series of N1-substituted derivatives of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been prepared as constrained analogs of gamma-substituted glutamic acids and examined for their effects at recombinant metabotropic glutamate receptor (mGluR) subtypes in vitro. Appropriate substitution of the N1 position of 2R,4R-APDC resulted in the identification of a number of selective group II mGluR antagonists.

MeSH terms

  • Humans
  • Hydrolysis
  • Phosphatidylinositol Phosphates / metabolism
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis
  • Proline / chemistry
  • Proline / pharmacology
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Recombinant Proteins / antagonists & inhibitors
  • Stereoisomerism
  • Structure-Activity Relationship


  • 4-aminopyrrolidine-2,4-dicarboxylic acid
  • Phosphatidylinositol Phosphates
  • Receptors, Metabotropic Glutamate
  • Recombinant Proteins
  • Proline