Discovery of Allosteric Potentiators for the Metabotropic Glutamate 2 Receptor: Synthesis and Subtype Selectivity of N-(4-(2-Methoxyphenoxy)phenyl)-N-(2,2,2− trifluoroethylsulfonyl)pyrid-3-ylmethylamine
| Autor: | G. Erik Jagdmann, Joseph P. Tizzano, David O. Callagaro, Darryle D. Schoepp, Michael P. Johnson, Thomas H. Large, James A. Monn, Thomas C. Britton, Melvyn Baez |
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| Rok vydání: | 2003 |
| Předmět: |
Reflex
Startle Pyridines Stereochemistry Pharmacology Receptors Metabotropic Glutamate Structure-Activity Relationship Allosteric Regulation Drug Discovery Excitatory Amino Acid Agonists Animals Humans Cells Cultured Sulfonamides Metabotropic glutamate receptor 5 Chemistry Metabotropic glutamate receptor 4 Metabotropic glutamate receptor 7 Metabotropic glutamate receptor 6 Drug Synergism Rats Kinetics Anti-Anxiety Agents Metabotropic glutamate receptor Molecular Medicine Metabotropic glutamate receptor 1 Calcium Metabotropic glutamate receptor 3 Metabotropic glutamate receptor 2 |
| Zdroj: | Journal of Medicinal Chemistry. 46:3189-3192 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | This report describes recently discovered novel allosteric modulators of metabotropic glutamate2 (mGlu2) receptors. These pyridylmethylsulfonamides (e.g., 3) potentiate glutamate, shifting agonist potency by 2-fold. This effect was specific for mGlu2 (vs mGlu1,3-8 receptors). Also, 3 failed to potentiate a chimeric mGlu2/1 receptor, demonstrating the mGlu2 transmembrane region's critical involvement. In a fear-potentiated startle model, 3 showed anxiolytic activity that was prevented by mGlu2/3 antagonist pretreatment. Thus, these pyridylmethylsulfonamides represent the first mGlu2 receptor potentiators discovered. |
| Databáze: | OpenAIRE |
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