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7-(1,1-二甲基乙基)-6-(2-乙基-2H-1,2,4-三唑-3-基甲氧基)-3-(2-氟苯基)-1,2,4-三唑并[4,3-b]哒嗪：一种功能选择性γ-氨基丁酸(A)(GABA(A))α2/α3亚型选择性激动剂，在动物模型中表现出强效抗焦虑活性但无镇静作用。

7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activity but is not sedating in animal models.

作者信息

Carling Robert W, Madin Andrew, Guiblin Alec, Russell Michael G N, Moore Kevin W, Mitchinson Andrew, Sohal Bindi, Pike Andrew, Cook Susan M, Ragan Ian C, McKernan Ruth M, Quirk Kathleen, Ferris Pushpinder, Marshall George, Thompson Sally Ann, Wafford Keith A, Dawson Gerard R, Atack John R, Harrison Timothy, Castro José L, Street Leslie J

机构信息

Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.

出版信息

J Med Chem. 2005 Nov 17;48(23):7089-92. doi: 10.1021/jm058034a.

DOI:10.1021/jm058034a
PMID:16279764
Abstract

There is increasing evidence that compounds with selectivity for gamma-aminobutyric acid(A) (GABA(A)) alpha2- and/or alpha3-subtypes may retain the desirable anxiolytic activity of nonselective benzodiazepines but possess an improved side effect profile. Herein we describe a novel series of GABA(A) alpha2/alpha3 subtype-selective agonists leading to the identification of the development candidate 17, a nonsedating anxiolytic in preclinical animal assays.

摘要

越来越多的证据表明，对γ-氨基丁酸A（GABA(A)）α2和/或α3亚型具有选择性的化合物可能保留非选择性苯二氮䓬类药物理想的抗焦虑活性，但副作用更少。在此，我们描述了一系列新型的GABA(A)α2/α3亚型选择性激动剂，从中鉴定出了研发候选药物17，它在临床前动物试验中是一种无镇静作用的抗焦虑药。

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