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

  • J Med Chem. 2011 Feb 24;54(4):1106-10. doi: 10.1021/jm101271s.
Darren W Engers  1 ,  Julie R Field ,  Uyen Le ,  Ya Zhou ,  Julie D Bolinger ,  Rocio Zamorano ,  Anna L Blobaum ,  Carrie K Jones ,  Satyawan Jadhav ,  C David Weaver ,  P Jeffrey Conn ,  Craig W Lindsley ,  Colleen M Niswender ,  Corey R Hopkins
Affiliations
  • 1. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
PMID: 21247167 DOI: 10.1021/jm101271s
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.

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