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Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats.

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.

SUBMITTER: Engers DW

PROVIDER: S-EPMC3166797 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats.

Engers Darren W DW Field Julie R JR Le Uyen U Zhou Ya Y Bolinger Julie D JD Zamorano Rocio R Blobaum Anna L AL Jones Carrie K CK Jadhav Satyawan S Weaver C David CD Conn P Jeffrey PJ Lindsley Craig W CW Niswender Colleen M CM Hopkins Corey R CR

Journal of medicinal chemistry 20110119 4

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. ...[more]

PMID: 21247167

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