title: Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs).
abstract: 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.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Darren W
authors.initials: DW
authors.lastname: Engers
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Niswender
authors.forename: C David
authors.initials: CD
authors.lastname: Weaver
authors.forename: Satyawan
authors.initials: S
authors.lastname: Jadhav
authors.forename: Usha N
authors.initials: UN
authors.lastname: Menon
authors.forename: Rocio
authors.initials: R
authors.lastname: Zamorano
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: Corey R
authors.initials: CR
authors.lastname: Hopkins
mesh_terms: 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
chemical_list: D000577:Amides; D018094:Receptors, Metabotropic Glutamate; C108823:metabotropic glutamate receptor 4