3,4-Dihydronaphthalen-1(2H)-ones: novel ligands for the benzodiazepine site of α5-containing GABAA receptors

A series of substituted 3,4-dihydronaphthalen-1(2H)-ones with high binding affinity for the benzodiazepine site of GABAA receptors containing the α5-subunit has been identified. These compounds have consistently higher binding affinity for the GABAA α5 receptor subtype over the other benzodiazepine-sensitive GABAA receptor subtypes (α1, α2 and α3). Compounds with a range of efficacies for the benzodiazepine site of α5-containing GABAA receptors were identified, including the α5 inverse agonist 3,3-dimethyl-8-methylthio-5-(pyridin-2-yl)-3,4-dihydronaphthalen-1(2H)-one 22 and the α5 agonist 8-ethylthio-3-methyl-5-(1-oxidopyridin-2-yl)-3,4-dihydronaphthalen-1(2H)-one 19.