Synthesis and pharmacological characterisation of 2,4-dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists

Bioorg Med Chem. 2003 Jan 17;11(2):171-83. doi: 10.1016/s0968-0896(02)00424-8.

Abstract

Metabotropic glutamate receptors (mGluRs) are an unusual family of G-protein coupled receptor (GPCR), and are characterised by a large extracellular N-terminal domain that contains the glutamate binding site. We have identified a new class of non-competitive metabotropic glutamate receptor 1 (mGluR1) antagonists, 2,4-dicarboxy-pyrroles which are endowed with nanomolar potency. They interact within the 7 transmembrane (7TM) domain of the receptor and show antinociceptive properties when tested in a number of different animal models.

MeSH terms

  • Analgesics, Non-Narcotic / chemical synthesis*
  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • CHO Cells
  • Combinatorial Chemistry Techniques
  • Cricetinae
  • Electrophysiology / methods
  • Humans
  • Inhibitory Concentration 50
  • Pain Measurement / drug effects
  • Protein Binding
  • Protein Structure, Tertiary
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacology*
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / chemistry
  • Receptors, Metabotropic Glutamate / genetics
  • Recombinant Fusion Proteins / antagonists & inhibitors
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Spinal Cord / drug effects
  • Spinal Cord / physiology
  • Structure-Activity Relationship
  • Xenopus laevis

Substances

  • Analgesics, Non-Narcotic
  • Pyrroles
  • Receptors, Metabotropic Glutamate
  • Recombinant Fusion Proteins
  • metabotropic glutamate receptor type 1