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 repre...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2010-09, Vol.20 (17), p.5175-5178
Hauptverfasser:	ENGERS, Darren W, GENTRY, Patrick R, WILLIAMS, Richard, BOLINGER, Julie D, WEAVER, C. David, MENON, Usha N, CONN, P. Jeffrey, LINDSLEY, Craig W, NISWENDER, Colleen M, HOPKINS, Corey R
Format:	Artikel
Sprache:	eng
Schlagworte:	Allosteric Regulation Aniline Compounds - chemical synthesis Aniline Compounds - chemistry Aniline Compounds - pharmacokinetics Aniline Compounds - pharmacology Biological and medical sciences Glutamatergic system (aspartate and other excitatory aminoacids) Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Receptors, Metabotropic Glutamate - drug effects Structure-Activity Relationship Sulfonamides - chemical synthesis Sulfonamides - chemistry Sulfonamides - pharmacokinetics Sulfonamides - pharmacology
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Zusammenfassung:	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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2010.07.007