Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005 - present)

Expert Opin Ther Pat. 2015 Jan;25(1):69-90. doi: 10.1517/13543776.2014.983899. Epub 2014 Dec 1.


Introduction: This review focuses on the medicinal chemistry efforts directed toward the identification of competitive and noncompetitive antagonists of glutamate at group II metabotropic glutamate receptors (mGluRII: mGlu2/3 and mGlu2). This class of compounds holds promise for the treatment of CNS disorders such as major depression, cognitive deficits and sleep-wake disorders, and several pharmaceutical companies are advancing mGluRII antagonists from discovery research into clinical development.

Area covered: This review article covers for the first time the patent applications that were published on mGlu2/3 orthosteric and allosteric antagonists between January 2005 and September 2014, with support from the primary literature, posters and oral communications from international congresses. Patent applications published prior to 2005 for which compositions of matter were largely described in peer review articles are briefly discussed with main findings.

Expert opinion: Recent advances in the prodrug approach of novel mGlu2/3 orthosteric antagonists combined with the design of novel mGlu2/3 and mGlu2 negative allosteric modulators provide new therapeutic opportunities for neurologic and psychiatric disorders.

Keywords: autism; cognitive deficits; glutamate antagonists; mGlu2; mGlu2/3; major depression; metabotropic glutamate receptor 2/3; negative allosteric modulator; orthosteric ligands; sleep-wake disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System Diseases / drug therapy*
  • Central Nervous System Diseases / metabolism
  • Drug Design
  • Drug Industry / legislation & jurisprudence*
  • Excitatory Amino Acid Antagonists / chemistry
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Humans
  • Molecular Structure
  • Patents as Topic*
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / chemistry
  • Receptors, Metabotropic Glutamate / metabolism
  • Signal Transduction / drug effects
  • Structure-Activity Relationship


  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3