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.
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.
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
Darren W
DW
Engers
Julie R
JR
Field
Uyen
U
Le
Ya
Y
Zhou
Julie D
JD
Bolinger
Rocio
R
Zamorano
Anna L
AL
Blobaum
Carrie K
CK
Jones
Satyawan
S
Jadhav
C David
CD
Weaver
P Jeffrey
PJ
Conn
Craig W
CW
Lindsley
Colleen M
CM
Niswender
Corey R
CR
Hopkins
D000494:Allosteric Regulation; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016466:CHO Cells; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010847:Picolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013329:Structure-Activity Relationship
D010847:Picolines; D018094:Receptors, Metabotropic Glutamate; C108823:metabotropic glutamate receptor 4
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