2,4-Dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists: an exploration of the role of the pyrrolic scaffold

Farmaco. 2003 Oct;58(10):1005-9. doi: 10.1016/S0014-827X(03)00112-5.

Abstract

Following the disclosure of 3-(1,2,2-trimethylpropyl) 4-[3,5-dimethyl-2-propyloxycarbonyl]pyrrolecarboxylate as a potent and selective mGluR1 non-competitive antagonist, the role and the importance of the pyrrole template were investigated. Different aromatic moieties were investigated as possible bio-isosteric replacement of the original scaffold and some of them were shown to be partially able to mimic the properties of the original pyrrole ring.

Publication types

  • Comparative Study

MeSH terms

  • Analgesics, Non-Narcotic / chemical synthesis*
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology
  • Binding, Competitive / drug effects
  • CHO Cells
  • Cricetinae
  • Esters / chemical synthesis
  • Esters / pharmacology
  • Inhibitory Concentration 50
  • Mice
  • Nociceptors / drug effects
  • Pain Measurement
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacology
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / chemistry
  • Receptors, Metabotropic Glutamate / genetics
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Structure-Activity Relationship
  • Thiophenes / chemistry
  • Thiophenes / pharmacology

Substances

  • Analgesics, Non-Narcotic
  • Benzene Derivatives
  • Esters
  • Pyrroles
  • Receptors, Metabotropic Glutamate
  • Thiophenes
  • metabotropic glutamate receptor type 1