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

doi:10.1016/j.bmcl.2010.03.089

Bioorganic & Medicinal Chemistry Letters

Volume 20, Issue 10, 15 May 2010, Pages 3129-3133

https://doi.org/10.1016/j.bmcl.2010.03.089 Get rights and content

Abstract

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.

Graphical abstract

Hit to lead optimization of oxazolidinones as positive allosteric modulators of mGluR2 is described. An optimized lead compound was found to be brain penetrant and active in a rat ketamine-induced hyperlocomotion model for antipsychotic activity.

Section snippets

Acknowledgments

We thank Ziqiang Wang for chiral separations of intermediates to give 34 and 35.

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

Abstract

Graphical abstract

Section snippets

Acknowledgments

Schizophr. Res.

Schizophr. Res.

Schizophr. Res.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem.

Arch. Gen. Psychiatry

N. Eng. J. Med.

Curr. Drug Targets CNS Neurol. Disord.

Mol. Interventions

J. Pharmacol. Exp. Ther.

Science