Design, synthesis and evaluation of 5-substituted 1-H-tetrazoles as potent anticonvulsant agents

被引：6

作者：

Liao, Ai-Mei ^{[1
,4
]}

Wang, Tiantian ^{[2
,3
]}

Cai, Bangrong ^{[1
]}

Jin, Yi ^{[2
,3
]}

Cheon, Seunghoon ^{[1
]}

Chun, ChangJu ^{[1
]}

Wang, Zengtao ^{[2
]}

机构：

[1] Chonnam Natl Univ, Res Inst Drug Dev, Coll Pharm, 77 Yongbong Ro, Gwangju 61186, South Korea

[2] JiangXi Univ Tradit Chinese Med, Dept Med Chem, Coll Pharm, Nanchang 330004, Jiangxi, Peoples R China

[3] Natl Pharmaceut Engn Ctr Solid Preparat Chinese H, Nanchang 330006, Jiangxi, Peoples R China

[4] Hefei Normal Univ, Sch Life Sci, Hefei 230601, Peoples R China

来源：

ARCHIVES OF PHARMACAL RESEARCH | 2017年 / 40卷 / 04期

关键词：

Synthesis; 5-Substituted; 1-H-tetrazoles; Anticonvulsant; ANTIEPILEPTIC DRUG DEVELOPMENT; IDENTIFICATION; 1H-TETRAZOLES; DISCOVERY; GLUTAMATE;

D O I：

10.1007/s12272-016-0881-y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 5-substituted 1-H-tetrazoles were designed and synthesized as potent anticonvulsant agents. Their preliminary anticonvulsant activities were evaluated using maximal electroshock and subcutaneous pentylenetetrazole (scPTZ) seizure tests. Neurotoxicity was determined using rotarod test. The results indicated that the compound 2j in scPTZ model exhibited the ED50 values of 83.3 mg/kg, superior to the standard drug ethosuximide with the maximum activity. In addition, compound 2k showed the most potent activity in MES model with ED50 value of 9.6 mg/kg and TD50 value of 189.5 mg/kg after intraperitoneal injection in mice, and displayed a high protective index (TD50/ED50) of 19.7 compared to reference antiepileptic drugs.

引用

页码：435 / 443

页数：9

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