Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)

J Med Chem. 2009 Jul 23;52(14):4115-8. doi: 10.1021/jm9005065.

Abstract

We report the synthesis and evaluation of a series of heterobiaryl amides as positive allosteric modulators of mGluR4. Compounds 9b and 9c showed submicromolar potency at both human and rat mGluR4. In addition, both 9b and 9c were shown to be centrally penetrant in rats using nontoxic vehicles, a major advance for the mGluR4 field.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Amides / administration & dosage
  • Amides / chemistry*
  • Amides / pharmacokinetics
  • Amides / pharmacology*
  • Animals
  • Cell Line
  • Humans
  • Rats
  • Receptors, Metabotropic Glutamate / agonists*
  • Structure-Activity Relationship

Substances

  • Amides
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 4