6,7-Dihydro-2-benzothiophen-4(5H)-ones:: A novel class of GABA-A α5 receptor inverse agonists

被引：33

作者：

Chambers, MS ^{[1
]}

Atack, JR ^{[1
]}

Bromidge, FA ^{[1
]}

Broughton, HB ^{[1
]}

Cook, S ^{[1
]}

Dawson, GR ^{[1
]}

Hobbs, SC ^{[1
]}

Maubach, KA ^{[1
]}

Reeve, AJ ^{[1
]}

Seabrook, GR ^{[1
]}

Wafford, K ^{[1
]}

MacLeod, AM ^{[1
]}

机构：

[1] Merck Sharp & Dohme Ltd, Res Labs, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 06期

关键词：

D O I：

10.1021/jm010471b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：1176 / 1179

页数：4

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