Abstract
Structure-activity relationship studies on 3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile 2 led to the discovery of 2-(2-[3-(pyridin-3-yloxy)phenyl]-2H-tetrazol-5-yl)pyridine (10)-a highly potent and selective mGlu5 receptor antagonist with good brain penetration and in vivo receptor occupancy in rat and cross-species oral bioavailability.
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 / chemistry
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Anti-Anxiety Agents / pharmacokinetics*
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Biological Availability
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Dogs
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Dose-Response Relationship, Drug
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Haplorhini
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Molecular Structure
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Nitriles / chemistry
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Nitriles / pharmacokinetics*
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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 / chemistry*
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Tetrazoles / pharmacokinetics*
Substances
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2-(2-(3-(pyridin-3-yloxy)phenyl)-2H-tetrazol-5-yl)pyridine
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3-(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