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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.

journal of medicinal chemistry

Discovery, Synthesis, and Structure−Activity Relationship Development of a Series of <i>N</i>-(4-Acetamido)phenylpicolinamides as Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4 (mGlu<sub>4</sub>) with CNS Exposure in Rats

Discovery, Synthesis, and Structure−Activity Relationship Development of a Series of N-(4-Acetamido)phenylpicolinamides as Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4 (mGlu4) with CNS Exposure in Rats

Discovery, Synthesis, and Structure−Activity Relationship Development of a Series of N-(4-Acetamido)phenylpicolinamides as Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4 (mGlu₄) with CNS Exposure in Rats