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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.


AUTHORS

Engers DWDarren W , Field JR Julie R , Le U Uyen , Zhou Y Ya , Bolinger JD Julie D , Zamorano R Rocio , Blobaum AL Anna L , Jones CK Carrie K , Jadhav S Satyawan , Weaver CD C David , Conn PJ P Jeffrey , Lindsley CW Craig W , Niswender CM Colleen M , Hopkins CR Corey R . Journal of medicinal chemistry. 2011 2 24; 54(4). 1106-10

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.


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.