Abstract
Development of SAR in a 5-aryl-3-acylpyridinyl-pyrazoles and 1-aryl-4-acylpyridinyl imidazoles series of mGlu5 receptor negative allosteric modulators (mGluR5 NAMs) using a functional cell-based assay is described in this Letter. Analysis of the Ligand-lipophilic efficiency (LipE) of compounds provided new insight for the design of potent mGluR5 negative allosteric modulators with anti-depressant activities.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Allosteric Regulation / drug effects
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Amides / chemical synthesis
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Amides / chemistry
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Amides / pharmacology*
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Animals
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Binding Sites / drug effects
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Dose-Response Relationship, Drug
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Drug Discovery*
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HEK293 Cells
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry
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Imidazoles / pharmacology*
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Ligands
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Mice
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Models, Molecular
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Molecular Structure
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrazoles / pharmacology*
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Rats
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Amides
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GRM5 protein, human
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Grm5 protein, mouse
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Grm5 protein, rat
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Imidazoles
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Ligands
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Pyrazoles
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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pyrazole