title: 6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists.
abstract: 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 alpha5 receptor ligands during our search for alpha5 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 alpha5 inverse agonist.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. mark_chambers@merck.com
authors.forename: Mark S
authors.initials: MS
authors.lastname: Chambers
authors.forename: John R
authors.initials: JR
authors.lastname: Atack
authors.forename: Frances A
authors.initials: FA
authors.lastname: Bromidge
authors.forename: Howard B
authors.initials: HB
authors.lastname: Broughton
authors.forename: Susan
authors.initials: S
authors.lastname: Cook
authors.forename: Gerard R
authors.initials: GR
authors.lastname: Dawson
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Hobbs
authors.forename: Karen A
authors.initials: KA
authors.lastname: Maubach
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Reeve
authors.forename: Guy R
authors.initials: GR
authors.lastname: Seabrook
authors.forename: Keith
authors.initials: K
authors.lastname: Wafford
authors.forename: Angus M
authors.initials: AM
authors.lastname: MacLeod
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003071:Cognition; D058785:GABA-A Receptor Agonists; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: C452421:6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one; D058785:GABA-A Receptor Agonists; D007659:Ketones; D013844:Thiazoles; D013876:Thiophenes