Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

Darren W Engers; Patrick R Gentry; Richard Williams; Julie D Bolinger; C David Weaver; Usha N Menon; P Jeffrey Conn; Craig W Lindsley; Colleen M Niswender; Corey R Hopkins

doi:10.1016/j.bmcl.2010.07.007

Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5175-8. doi: 10.1016/j.bmcl.2010.07.007. Epub 2010 Jul 8.

Authors

Darren W Engers¹, Patrick R Gentry, Richard Williams, Julie D Bolinger, C David Weaver, Usha N Menon, P Jeffrey Conn, Craig W Lindsley, Colleen M Niswender, Corey R Hopkins

Affiliation

¹ Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Allosteric Regulation
Aniline Compounds / chemical synthesis
Aniline Compounds / chemistry*
Aniline Compounds / pharmacokinetics
Aniline Compounds / pharmacology*
Receptors, Metabotropic Glutamate / drug effects*
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacokinetics
Sulfonamides / pharmacology*

Substances

Aniline Compounds
Receptors, Metabotropic Glutamate
Sulfonamides
metabotropic glutamate receptor 4

Abstract

Publication types

MeSH terms

Substances

Grants and funding