Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS).
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.
Engers
Darren W
DW
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Gentry
Patrick R
PR
Williams
Richard
R
Bolinger
Julie D
JD
Weaver
C David
CD
Menon
Usha N
UN
Conn
P Jeffrey
PJ
Lindsley
Craig W
CW
Niswender
Colleen M
CM
Hopkins
Corey R
CR
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*
D000814:Aniline Compounds; D018094:Receptors, Metabotropic Glutamate; D013449:Sulfonamides; C108823:metabotropic glutamate receptor 4