Discovery and in vitro and in vivo profiles of 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as novel class of an orally active metabotropic glutamate receptor 1 (mGluR1) antagonist

Bioorg Med Chem Lett. 2009 Sep 15;19(18):5464-8. doi: 10.1016/j.bmcl.2009.07.097. Epub 2009 Jul 23.

Abstract

We identified 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide 27 as a potent mGluR1 antagonist. The compound possessed excellent subtype selectivity and good PK profile in rats. It also demonstrated relatively potent antipsychotic-like effects in several animal models. Suitable for development as a PET tracer, compound 27 would have great potential for elucidation of mGluR1 functions in human.

MeSH terms

  • Animals
  • Antipsychotic Agents / chemistry
  • Antipsychotic Agents / pharmacokinetics*
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Benzamides / chemistry
  • Benzamides / pharmacokinetics*
  • Benzamides / pharmacology*
  • Benzamides / therapeutic use
  • Humans
  • Mice
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / metabolism*
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Benzamides
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • N-methylbenzamide