Abstract
We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl)ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl)ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylene / analogs & derivatives*
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Acetylene / chemistry
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Acetylene / pharmacology
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Animals
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Binding, Competitive / drug effects
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Cells, Cultured
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Ligands
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Mice
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Molecular Structure
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Pyridines / chemistry*
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Pyridines / 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
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Thiazoles / chemistry*
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Thiazoles / pharmacology
Substances
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Grm5 protein, mouse
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Grm5 protein, rat
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Ligands
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Pyridines
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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Thiazoles
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phenylacetylene
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Acetylene