3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts

Bioorg Med Chem Lett. 2010 May 15;20(10):3129-33. doi: 10.1016/j.bmcl.2010.03.089. Epub 2010 Mar 31.


Hit to lead optimization of (5R)-5-hexyl-3-phenyl-1,3-oxazolidin-2-one as a positive allosteric modulator of mGluR2 is described. Improvements in potency and metabolic stability were achieved through SAR on both ends of the oxazolidinone. An optimized lead compound was found to be brain penetrant and active in a rat ketamine-induced hyperlocomotion model for antipsychotic activity.

MeSH terms

  • Allosteric Regulation
  • Animals
  • Antipsychotic Agents
  • Ketamine / toxicity
  • Oxazolidinones / chemical synthesis
  • Oxazolidinones / chemistry*
  • Oxazolidinones / pharmacology
  • Rats
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / metabolism*
  • Schizophrenia / drug therapy*
  • Structure-Activity Relationship


  • Antipsychotic Agents
  • Oxazolidinones
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Ketamine