3-Methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester: an exploration of the C-2 position. Part I

Farmaco. 2004 Mar;59(3):175-83. doi: 10.1016/j.farmac.2003.12.005.

Abstract

Following the recent disclosure of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester, a potent and selective mGluR1 non-competitive antagonist, we report here a detailed exploration of the C-2 position of this scaffold with the preparation of differently substituted amides. Great improvement of the pharmacokinetic properties has been achieved through this exercise.

MeSH terms

  • Amides / chemical synthesis
  • Amides / pharmacokinetics
  • Animals
  • Azides / chemical synthesis
  • Azides / pharmacokinetics
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Esters / chemical synthesis*
  • Esters / pharmacology*
  • Hydroxamic Acids / chemical synthesis
  • Hydroxamic Acids / pharmacokinetics
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mice
  • Molecular Conformation
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacology*
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Solubility
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship

Substances

  • 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester
  • Amides
  • Azides
  • Esters
  • Hydroxamic Acids
  • Indicators and Reagents
  • Pyrroles
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1