| 3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats. | |
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MedLine Citation:
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PMID: 20598884 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Development of SAR in a 3-cyano-5-fluoro-N-arylbenzamide series of non-competitive antagonists of mGlu(5) using a functional cell-based assay is described in this Letter. Further characterization of selected potent compounds in in vitro assays designed to measure their metabolic stability and protein binding is also presented. Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples. |
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Authors:
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Andrew S Felts; Stacey R Lindsley; Jeffrey P Lamb; Alice L Rodriguez; Usha N Menon; Satyawan Jadhav; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-06-15 |
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 Aug |
Date Detail:
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Created Date: 2010-07-16 Completed Date: 2010-11-23 Revised Date: 2011-09-13 |
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: 4390-4 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Allosteric Regulation Animals Benzamides / chemical synthesis, chemistry*, pharmacokinetics Blood Proteins / metabolism Brain / metabolism Microsomes, Liver / metabolism Protein Binding Rats Receptors, Metabotropic Glutamate / antagonists & inhibitors*, chemistry, metabolism Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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R01 DA023947-01/DA/NIDA NIH HHS; R01 DA023947-01/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Benzamides; 0/Blood Proteins; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 5 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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