Phyarmacokinetics and metabolism studies on (3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy) pyrazolo[1,5-d][1,2,4]triazine, a functionally selective GABAA α5 inverse agonist for cognitive dysfunction
Phyarmacokinetics and metabolism studies on (3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy) pyrazolo[1,5-d][1,2,4]triazine, a functionally selective GABAA α5 inverse agonist for cognitive dysfunction
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DOI：
10.1016/j.bmcl.2005.11.012
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发表时间：
2006-02-15
影响因子：
2.7
通讯作者：
MacLeod, AM
中科院分区：
文献类型：
--
作者：
Jones, P;Atack, JR;MacLeod, AM
（3-叔丁基-7-（5-甲基异恶唑-3-基）-2-（1-甲基-1H-1，2，4-三唑-5-基甲氧基）吡唑并[1，5-d][1，2，4]三嗪（1）最近被鉴定为GABA（A）α 5受体苯二氮卓位点的功能选择性反向激动剂，并增强动物认知模型的表现。已充分表征了该化合物在大鼠体内的代谢途径，通过合成确认了主要代谢产物的身份，并评价了其生物学特征。已经观察到吡唑并[1，5-d][1，2，4]三嗪核心通过醛氧化酶不寻常地氧化为相应的吡唑并[1，5-d][1，2，4]三嗪-4（5 H）-酮支架。(c)2005爱思唯尔有限公司保留所有权利。
(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (1) was recently identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha 5 receptors and enhances performance in animal models of cognition. The routes of metabolism of this compound in vivo in rat have been well characterised, the identities of the major metabolites are confirmed by synthesis and their biological profiles were evaluated. An unusual oxidation of the pyrazolo[1,5-d][1,2,4]triazine core to the corresponding pyrazolo[1,5-d][1,2,4]triazin-4(5H)-one scaffold by aldehyde oxidase has been observed. (c) 2005 Elsevier Ltd. All rights reserved.