Discovery and SAR of a novel series of non-MPEP site mGlu₅ PAMs based on an aryl glycine sulfonamide scaffold

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7388-92. doi: 10.1016/j.bmcl.2012.10.068. Epub 2012 Oct 23.

Abstract

Herein we report the discovery and SAR of a novel series of non-MPEP site metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs) based on an aryl glycine sulfonamide scaffold. This series represents a rare non-MPEP site mGlu(5) PAM chemotype.

Publication types

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

MeSH terms

  • Allosteric Regulation / drug effects
  • Animals
  • Binding Sites / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Glycine / analogs & derivatives
  • Glycine / chemistry
  • Glycine / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Rats
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / chemistry
  • Receptors, Metabotropic Glutamate / metabolism*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Sulfonamides
  • Glycine