Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4)

Bioorg Med Chem Lett. 2009 Sep 1;19(17):4967-70. doi: 10.1016/j.bmcl.2009.07.072. Epub 2009 Jul 18.

Abstract

This Letter describes the synthesis and SAR of the novel positive allosteric modulator, VU0155041, a compound that has shown in vivo efficacy in rodent models of Parkinson's disease. The synthesis takes advantage of an iterative parallel synthesis approach to rapidly synthesize and evaluate a number of analogs of VU0155041.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation / drug effects
  • Allosteric Site
  • Anilides / chemical synthesis*
  • Anilides / chemistry
  • Anilides / pharmacology
  • Animals
  • Cyclohexanecarboxylic Acids / chemical synthesis*
  • Cyclohexanecarboxylic Acids / chemistry
  • Cyclohexanecarboxylic Acids / pharmacology
  • Disease Models, Animal
  • Parkinson Disease / drug therapy
  • Rats
  • Receptors, Metabotropic Glutamate / chemistry*
  • Receptors, Metabotropic Glutamate / metabolism
  • Structure-Activity Relationship

Substances

  • Anilides
  • Cyclohexanecarboxylic Acids
  • Receptors, Metabotropic Glutamate
  • VU 0155041
  • metabotropic glutamate receptor 4