title: Biphenyl-indanones: allosteric potentiators of the metabotropic glutamate subtype 2 receptor.
abstract: We have identified and synthesized a series of biphenyl-carboxylic acid indanones as allosteric potentiators of the metabotropic glutamate receptor 2. Structure-activity relationship studies directed toward improving the potency and the brain to plasma ratio of the initial lead led to the discovery of 5 and 23 (EC50=111 and 5 nM, respectively).
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. celine_bonnefous@yahoo.com
authors.forename: Céline
authors.initials: C
authors.lastname: Bonnefous
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vernier
authors.forename: John H
authors.initials: JH
authors.lastname: Hutchinson
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gardner
authors.forename: Merryl
authors.initials: M
authors.lastname: Cramer
authors.forename: Joyce K
authors.initials: JK
authors.lastname: James
authors.forename: Blake A
authors.initials: BA
authors.lastname: Rowe
authors.forename: Lorrie P
authors.initials: LP
authors.lastname: Daggett
authors.forename: Hervé
authors.initials: H
authors.lastname: Schaffhauser
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Kamenecka
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D001923:Brain Chemistry; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007189:Indans / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D001713:Biphenyl Compounds; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D016244:Guanosine 5'-O-(3-Thiotriphosphate)