Abstract
Herein we report the discovery, synthesis, and evaluation of a series of N-(4-acetamido)-phenylpicolinamides as positive allosteric modulators of mGlu(4). Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats.
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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Allosteric Regulation
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Animals
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Brain / drug effects
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Brain / metabolism
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CHO Cells
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Central Nervous System / drug effects*
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Central Nervous System / metabolism*
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Cricetinae
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Cricetulus
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Humans
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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Picolines / chemical synthesis
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Picolines / chemistry*
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Picolines / pharmacokinetics
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Picolines / pharmacology*
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Rats
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Receptors, Metabotropic Glutamate / metabolism*
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Structure-Activity Relationship
Substances
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Picolines
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor 4