Abstract
Structure-activity relationship studies performed around 3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile for the purpose of developing novel mGlu5 receptor antagonists are described. Synthesis of a series of four-ring tetrazoles led to the discovery of 3-[3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)phenyl]-4-methylpyridine, a highly potent, brain penetrant, azole-based mGlu5 receptor antagonist.
MeSH terms
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Administration, Oral
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Animals
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Anti-Anxiety Agents / administration & dosage
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Anti-Anxiety Agents / chemical synthesis
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Anti-Anxiety Agents / pharmacokinetics*
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Biological Availability
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Molecular Structure
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacokinetics
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacokinetics
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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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Tetrazoles / chemical synthesis*
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Tetrazoles / chemistry
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Tetrazoles / pharmacokinetics
Substances
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3-(3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)phenyl)-4-methylpyridine
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3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile
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Anti-Anxiety Agents
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Nitriles
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Pyridines
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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Tetrazoles