Structure-activity relationships in a novel series of 7-substituted-aryl quinolines and 5-substituted-aryl benzothiazoles at the metabotropic glutamate receptor subtype 5

Bioorg Med Chem. 2010 May 1;18(9):3026-35. doi: 10.1016/j.bmc.2010.03.053. Epub 2010 Mar 27.

Abstract

The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in numerous neuropsychiatric disorders including addiction. We have discovered that the rigid diaryl alkyne template, derived from the potent and selective noncompetitive mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), can serve to guide the design of novel quinoline analogues and pharmacophore optimization has resulted in potent mGluR5 noncompetitive antagonists (EC(50) range 60-100 nM) in the quinoline series.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Benzothiazoles / chemistry*
  • Brain / cytology
  • Cell Line
  • Drug Design
  • Excitatory Amino Acid Antagonists* / chemistry
  • Excitatory Amino Acid Antagonists* / pharmacology
  • Inhibitory Concentration 50
  • Molecular Structure
  • Pyridines* / chemistry
  • Pyridines* / pharmacology
  • Quinolines / chemistry*
  • Rats
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / chemistry*
  • Structure-Activity Relationship

Substances

  • Benzothiazoles
  • Excitatory Amino Acid Antagonists
  • Grm5 protein, rat
  • Pyridines
  • Quinolines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • 6-methyl-2-(phenylethynyl)pyridine
  • benzothiazole