An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA α5 receptors with cognition enhancing properties

被引：98

作者：

Chambers, MS ^{[1
]}

Atack, JR ^{[1
]}

Carling, RW ^{[1
]}

Collinson, N ^{[1
]}

Cook, SM ^{[1
]}

Dawson, GR ^{[1
]}

Ferris, P ^{[1
]}

Hobbs, SC ^{[1
]}

O'Connor, D ^{[1
]}

Marshall, G ^{[1
]}

Rycroft, W ^{[1
]}

MacLeod, AM ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 24期

关键词：

D O I：

10.1021/jm040863t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1-H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d] [1,2,4]triazine (13) has been identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors. 13 is orally bioavailable, readily penetrates the CNS, and enhances performance in animal models of cognition. It does not exhibit the convulsant, proconvulsant, or anxiogenic activity associated with nonselective GABAA inverse agonists.

引用

页码：5829 / 5832

页数：4

共 41 条

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