Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs).
We report the synthesis and evaluation of a series of heterobiaryl amides as positive allosteric modulators of mGluR4. Compounds 9b and 9c showed submicromolar potency at both human and rat mGluR4. In addition, both 9b and 9c were shown to be centrally penetrant in rats using nontoxic vehicles, a major advance for the mGluR4 field.
Engers
Darren W
DW
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Niswender
Colleen M
CM
Weaver
C David
CD
Jadhav
Satyawan
S
Menon
Usha N
UN
Zamorano
Rocio
R
Conn
P Jeffrey
PJ
Lindsley
Craig W
CW
Hopkins
Corey R
CR
D000494:Allosteric Regulation; D000577:Amides / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006801:Humans; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013329:Structure-Activity Relationship
D000577:Amides; D018094:Receptors, Metabotropic Glutamate; C108823:metabotropic glutamate receptor 4