title: 3,4-Dihydronaphthalen-1(2H)-ones: novel ligands for the benzodiazepine site of alpha5-containing GABAA receptors.
abstract: A series of substituted 3,4-dihydronaphthalen-1(2H)-ones with high binding affinity for the benzodiazepine site of GABAA receptors containing the alpha5-subunit has been identified. These compounds have consistently higher binding affinity for the GABAA alpha5 receptor subtype over the other benzodiazepine-sensitive GABAA receptor subtypes (alpha1, alpha2 and alpha3). Compounds with a range of efficacies for the benzodiazepine site of alpha5-containing GABAA receptors were identified, including the alpha5 inverse agonist 3,3-dimethyl-8-methylthio-5-(pyridin-2-yl)-3,4-dihydronaphthalen-1(2H)-one 22 and the alpha5 agonist 8-ethylthio-3-methyl-5-(1-oxidopyridin-2-yl)-3,4-dihydronaphthalen-1(2H)-one 19.
authors.affiliation: Merck, Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Szekeres
authors.forename: John R
authors.initials: JR
authors.lastname: Atack
authors.forename: Mark S
authors.initials: MS
authors.lastname: Chambers
authors.forename: Susan M
authors.initials: SM
authors.lastname: Cook
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Macaulay
authors.forename: Gopalan V
authors.initials: GV
authors.lastname: Pillai
authors.forename: Angus M
authors.initials: AM
authors.lastname: MacLeod
mesh_terms: D000495:Allosteric Site; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D001665:Binding Sites; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006801:Humans; D008024:Ligands; D009281:Naphthalenes / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008024:Ligands; D009281:Naphthalenes; D021122:Protein Subunits; D011963:Receptors, GABA-A; D001569:Benzodiazepines