3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts
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.
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Acknowledgments
We thank Ziqiang Wang for chiral separations of intermediates to give 34 and 35.
References and notes (25)
- et al.
Schizophr. Res.
(2008) - et al.
Schizophr. Res.
(2008) - et al.
Schizophr. Res.
(2006) - et al.
Bioorg. Med. Chem. Lett.
(2005) - et al.
Bioorg. Med. Chem. Lett.
(2009) - et al.
Bioorg. Med. Chem.
(2004) - et al.
Arch. Gen. Psychiatry
(1993) - et al.
N. Eng. J. Med.
(2005) - et al.
Curr. Drug Targets CNS Neurol. Disord.
(2002) - et al.
Mol. Interventions
(2008)
J. Pharmacol. Exp. Ther.
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