An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4901-5. doi: 10.1016/j.bmcl.2010.06.078. Epub 2010 Jun 25.

Abstract

A high-throughput screening campaign identified 4-((E)-styryl)-pyrimidin-2-ylamine (11) as a positive allosteric modulator of the metabotropic glutamate (mGlu) receptor subtype 4. An evaluation of the structure-activity relationships (SAR) of 11 is described and the efficacy of this compound in a haloperidol-induced catalepsy rat model following oral administration is presented.

MeSH terms

  • Administration, Oral
  • Allosteric Regulation
  • Animals
  • Catalepsy / chemically induced
  • Catalepsy / drug therapy
  • High-Throughput Screening Assays
  • Humans
  • Models, Animal
  • Motor Activity / physiology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / chemistry*
  • Receptors, Metabotropic Glutamate / metabolism
  • Structure-Activity Relationship
  • Styrenes / chemical synthesis
  • Styrenes / chemistry*
  • Styrenes / therapeutic use

Substances

  • 4-styrylpyrimidin-2-ylamine
  • Pyrimidines
  • Receptors, Metabotropic Glutamate
  • Styrenes
  • metabotropic glutamate receptor 4