2,4-Dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists: further characterization of 3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester and structure-activity relationships

Bioorg Med Chem Lett. 2003 Jul 7;13(13):2113-8. doi: 10.1016/s0960-894x(03)00396-2.

Abstract

Following the disclosure of 3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester [3,5-dimethyl PPP] as a potent and selective mGluR1 non-competitive antagonist, we report here further in vivo characterization of this important tool and disclose the investigation of the C-5 position, which led to very potent compounds.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Esters / chemical synthesis*
  • Esters / pharmacology
  • Excitatory Amino Acid Antagonists / chemical synthesis*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Indicators and Reagents
  • Morphine / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism
  • Nociceptors / drug effects
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacology
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Structure-Activity Relationship
  • Synaptic Transmission / drug effects
  • Thalamus / drug effects
  • Thalamus / metabolism

Substances

  • 3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester
  • Esters
  • Excitatory Amino Acid Antagonists
  • Indicators and Reagents
  • Pyrroles
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Morphine