title: Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 3: Identification and biological activity of indanone containing mGlu2 receptor potentiators.
abstract: We have identified and synthesized a series of phenyl-tetrazolyl and 4-thiopyridyl indanones as allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation, as well as PK properties, led to the discovery of 28 (EC50=186 nM), which displayed activity in a rodent model for schizophrenia.
authors.affiliation: Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. anthony_pinkerton@merck.com
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Pinkerton
authors.forename: Rowena V
authors.initials: RV
authors.lastname: Cube
authors.forename: John H
authors.initials: JH
authors.lastname: Hutchinson
authors.forename: Joyce K
authors.initials: JK
authors.lastname: James
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gardner
authors.forename: Blake A
authors.initials: BA
authors.lastname: Rowe
authors.forename: Hervé
authors.initials: H
authors.lastname: Schaffhauser
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rodriguez
authors.forename: Una C
authors.initials: UC
authors.lastname: Campbell
authors.forename: Lorrie P
authors.initials: LP
authors.lastname: Daggett
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vernier
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D007189:Indans / Q000493:pharmacokinetics / Q000494:pharmacology*; D008956:Models, Chemical; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012559:Schizophrenia / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D007189:Indans; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2