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.

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