Discovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators

Bioorg Med Chem Lett. 2013 Apr 1;23(7):2134-9. doi: 10.1016/j.bmcl.2013.01.116. Epub 2013 Feb 4.

Abstract

Development of SAR in a 5-aryl-3-acylpyridinyl-pyrazoles and 1-aryl-4-acylpyridinyl imidazoles series of mGlu5 receptor negative allosteric modulators (mGluR5 NAMs) using a functional cell-based assay is described in this Letter. Analysis of the Ligand-lipophilic efficiency (LipE) of compounds provided new insight for the design of potent mGluR5 negative allosteric modulators with anti-depressant activities.

MeSH terms

  • Allosteric Regulation / drug effects
  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Animals
  • Binding Sites / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • HEK293 Cells
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Ligands
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Rats
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Amides
  • GRM5 protein, human
  • Grm5 protein, mouse
  • Grm5 protein, rat
  • Imidazoles
  • Ligands
  • Pyrazoles
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • pyrazole