共 49 条
Synthesis and evaluation of the anticonvulsant activity of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4]thiazepine derivatives
被引:12
作者:
Deng, Xian-Qing
[1
,2
]
Song, Ming-Xia
[1
,2
]
Wang, Shi-Ben
[1
]
Quan, Zhe-Shan
[1
]
机构:
[1] Yanbian Univ, Coll Pharm, Yanji 133002, Jilin, Peoples R China
[2] Jinggangshan Univ, Coll Med, Jian 343009, Jiangxi, Peoples R China
基金:
中国国家自然科学基金;
关键词:
Anticonvulsant;
benzothiazepines;
maximal electroshock;
neurotoxicity;
triazole;
ANTIEPILEPTIC DRUGS;
ANTI-HIV;
ANTAGONISM;
ABSORPTION;
DISCOVERY;
EPILEPSY;
SEIZURES;
ANALOGS;
DESIGN;
ACID;
D O I:
10.3109/14756366.2013.776555
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Two series of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4] thiazepine derivatives (6a-q and 7a-q) were synthesized and evaluated for their anticonvulsant activity using the maximal electroshock (MES) method. All of the compounds prepared were effective in the MES screens. Among which, compound 7j was considered as the most promising one with an ED50 value of 26.3 mg/kg and a superior protective index value of 12.6. The potency of compound 7j against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid and bicuculline suggested that two different mechanisms of action might potentially be involved in its anticonvulsant activity, including the inhibition of voltage-gated ion channels and the modulation of GABAergic activity. A computational study was also conducted to predict the pharmacokinetic properties of the compounds prepared, with the results supporting the use of these compounds as a group of promising antiepileptic agents.
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页码:272 / 280
页数:9
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