207306-63-6Relevant academic research and scientific papers
Identification of a novel, selective GABAa α5 receptor inverse agonist which enhances cognition
Chambers, Mark S.,Atack, John R.,Broughton, Howard B.,Collinson, Neil,Cook, Susan,Dawson, Gerard R.,Hobbs, Sarah C.,Marshall, George,Maubach, Karen A.,Pillai, Goplan V.,Reeve, Austin J.,MacLeod, Angus M.
, p. 2227 - 2240 (2007/10/03)
In pursuit of a GABAA α5-subtype-selective inverse agonist to enhance cognition, a series of 6,7-dihydro-2-benzothiophen-4(5H)-ones has been identified as a novel class of GABAA receptor ligands. These thiophenes have higher binding affinity for the GABAA α5 receptor subtype compared to the GABAA α1, α2, and α3 subtypes, and several analogues exhibit high GABAA α5 receptor inverse agonism. 6,6-Dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2- benzothiophen-4(5H)-one (43) has been identified as a full inverse agonist at the GABAA α5 receptor and is functionally selective over the other major GABAA receptor subtypes. 43 readily penetrates into the CNS to give selective occupancy of GABAA α5 receptors. In addition, 43 enhances cognitive performance in rats in the delayed 'matching-to-place' Morris water maze test - a hippocampal-dependent memory task - without the convulsant or proconvulsant activity associated with nonselective, GABAA receptor inverse agonists.
6,7-Dihydro-2-benzothiophen-4(5H)-ones: A novel class of GABA-A α5 receptor inverse agonists
Chambers, Mark S.,Atack, John R.,Bromidge, Frances A.,Broughton, Howard B.,Cook, Susan,Dawson, Gerard R.,Hobbs, Sarah C.,Maubach, Karen A.,Reeve, Austin J.,Seabrook, Guy R.,Wafford, Keith,Ma, Angus M.
, p. 1176 - 1179 (2007/10/03)
Nonselective inverse agonists at the benzodiazepine binding site on the GABA-A chloride ion channel enhance cognitive performance in animals but cannot be used in the treatment of cognitive disorders because of anxiogenic and convulsant side effects. We have identified a novel series of GABA-A α5 receptor ligands during our search for α5 receptor inverse agonists as potential cognition enhancers. In particular, 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6, 7-dihydro-2-benzothiophen-4(5H)-one (26) has been identified as a functionally selective GABA-A α5 inverse agonist.
