| 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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MedLine Citation:
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PMID: 20409708 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Edward J Brnardic; Mark E Fraley; Robert M Garbaccio; Mark E Layton; John M Sanders; Chris Culberson; Marlene A Jacobson; Brian C Magliaro; Pete H Hutson; Julie A O'Brien; Sarah L Huszar; Jason M Uslaner; Kerry L Fillgrove; Cuyue Tang; Yuhsin Kuo; Sylvie M Sur; George D Hartman |
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Publication Detail:
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Type: Journal Article Date: 2010-03-31 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 20 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-04 Completed Date: 2010-08-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 3129-33 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. edward_brnardic@merck.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Allosteric Regulation Animals Antipsychotic Agents Ketamine / toxicity Oxazolidinones / chemical synthesis, chemistry*, pharmacology Rats Receptors, Metabotropic Glutamate / agonists, metabolism* Schizophrenia / drug therapy* Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Antipsychotic Agents; 0/Oxazolidinones; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 2; 6740-88-1/Ketamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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