Synthesis of Novel 8-alkylamino-5, 6-dihydro-4H-benzo[f] [1,2,4]triazolo [4,3-a]azepines as Anticonvulsant Agents

被引：4
作者：
Wu, Hui-Fan [1 ]
Han, Rong-Bi [1 ,2 ]
Jin, Chun-Zi [3 ]
Piao, Feng-Yu [1 ,2 ]
机构：
[1] Yanbian Univ, Coll Sci, Dept Chem, Yanji 133002, Jilin Province, Peoples R China
[2] Yanbian Univ, Minist Educ, Key Lab Nat Resources Changbai Mt & Funct Mol, Yanji 133002, Jilin Province, Peoples R China
[3] Petrochina, Packing Prod Plant Jilin Petrochem Co Ltd, Longtan 132022, Jilin, Peoples R China
来源：
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS | 2016年 / 15卷 / 10期
关键词：
Anticonvulsant activity; Benzotriazoloazepine; Synthesis; Triazole; Toxicity; ANTIEPILEPTIC DRUG DEVELOPMENT; GABA; RECOGNITION; RECEPTOR; ANALOGS; ACID;
D O I：
10.2174/1871527315666160321111211
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
A series of new 8-alkylamino-5, 6-dihydro-4H-benzo[f][1,2,4] triazolo [4,3-a] azepine derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. The results of these tests showed that 8-heptylamino-5,6-dihydro-4H-benzo[f][1,2,4] triazolo[4,3-a] azepine (7g) was the most promising compound, with median effective dose (ED50) of 19.0 mg/kg, and protective index (PI) value of 14.8 in the MES test, which is much higher than the PI value of the prototype antiepileptic drug carbamazepine (PI = 8.1), phenytoin (PI = 6.9), phenobarbital (PI = 3.2), and sodium valproate (PI = 1.6). The possible structure-activity relationship was discussed.
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收藏
页码：1333 / 1343
页数：11
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