title: Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS).
abstract: Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu(4) positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu(4) PAM reported to date.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Darren W
authors.initials: DW
authors.lastname: Engers
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Gentry
authors.forename: Richard
authors.initials: R
authors.lastname: Williams
authors.forename: Julie D
authors.initials: JD
authors.lastname: Bolinger
authors.forename: C David
authors.initials: CD
authors.lastname: Weaver
authors.forename: Usha N
authors.initials: UN
authors.lastname: Menon
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Niswender
authors.forename: Corey R
authors.initials: CR
authors.lastname: Hopkins
mesh_terms: D000494:Allosteric Regulation; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000814:Aniline Compounds; D018094:Receptors, Metabotropic Glutamate; D013449:Sulfonamides; C108823:metabotropic glutamate receptor 4