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

Basic Information

ID: ALA1157756

Journal: Bioorg Med Chem Lett

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

Authors: Brnardic EJ, Fraley ME, Garbaccio RM, Layton ME, Sanders JM, Culberson C, Jacobson MA, Magliaro BC, Hutson PH, O'Brien JA, Huszar SL, Uslaner JM, Fillgrove KL, Tang C, Kuo Y, Sur SM, Hartman GD.

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.

CiteXplore: 20409708

DOI: 10.1016/j.bmcl.2010.03.089

Patent ID: ┄