Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu 4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 17; pp. 5175 - 5178
• Main Authors: 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: Journal Article
• Language: English
• Published: Elsevier Ltd 01-09-2010
• Subjects: Functional high-throughput screen (HTS); Metabotropic glutamate receptor 4; mGlu; mGlu; Functional high-throughput screen (HTS); Metabotropic glutamate receptor 4
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.07.007

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.
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.