Discovery of a potent and brain penetrant mGluR5 positive allosteric modulator

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3275-8. doi: 10.1016/j.bmcl.2009.04.095. Epub 2009 Apr 24.

Abstract

This Letter describes the discovery of a novel series of mGluR5 positive allosteric modulators (PAMs). The lead compound, 11c, exhibits excellent potency (EC(50)=30 nM) in vitro, and reaches high brain levels in both rats and mice after oral administration.

MeSH terms

  • Administration, Oral
  • Alkynes / chemistry*
  • Alkynes / pharmacology
  • Allosteric Regulation
  • Animals
  • Brain / metabolism*
  • Drug Discovery
  • Heterocyclic Compounds / chemistry*
  • Heterocyclic Compounds / pharmacology
  • Mice
  • Rats
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / agonists*
  • Structure-Activity Relationship

Substances

  • Alkynes
  • Grm5 protein, mouse
  • Grm5 protein, rat
  • Heterocyclic Compounds
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate