3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts
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- 作者：Edward J. Brnardic ; Mark E. Fraley ; Robert M. Garbaccio ; Mark E. Layton ; John M. S ; ers ; Chris Culberson ; Marlene A. Jacobson ; Brian C. Magliaro ; Pete H. Hutson ; Julie A. O’ ; Brien ; Sarah L. Husza
- 关键词：mGluR2 ; Metabotropic glutamate receptors ; Positive allosteric modulator ; Schizophrenia ; Oxazolidinone ; Hit to lead
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2010
- 出版时间：15 May 2010
- 年：2010
- 卷：20
- 期：10
- 页码：3129-3133
- 全文大小：983 K
文摘
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.