title: Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005 - present).
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CEO, Pragma Therapeutics , 9 rue Ada Byron, Domaine de Chosal, Archamp Technopole, 74166 Saint-Julien-en-Genevois Cedex , France +33 6 79 85 37 06 ; sylvain.celanire@pragmatherapeutics.com.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Celanire
authors.forename: Iyassu
authors.initials: I
authors.lastname: Sebhat
authors.forename: Juergen
authors.initials: J
authors.lastname: Wichmann
authors.forename: Stanislas
authors.initials: S
authors.lastname: Mayer
authors.forename: Stephan
authors.initials: S
authors.lastname: Schann
authors.forename: Silvia
authors.initials: S
authors.lastname: Gatti
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D015195:Drug Design; D004345:Drug Industry / Q000331:legislation & jurisprudence*; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015394:Molecular Structure; D010330:Patents as Topic; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3
keywords: autism; cognitive deficits; glutamate antagonists; mGlu2; mGlu2/3; major depression; metabotropic glutamate receptor 2/3; negative allosteric modulator; orthosteric ligands; sleep-wake disorders