Discovery of Triazenyl Triazoles as Nav1.1 Channel Blockers for Treatment of Epilepsy.
Discovery of Triazenyl Triazoles as Nav1.1 Channel Blockers for Treatment of Epilepsy.
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DOI：
10.1016/j.bmcl.2022.128946
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发表时间：
2022-08
影响因子：
2.7
通讯作者：
Xianjin Zhou;Linwei Zeng;Yi Wang;Ceng-lin Xu;Zhong Chen;Sunliang Cui
中科院分区：
文献类型：
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作者：
Xianjin Zhou;Linwei Zeng;Yi Wang;Ceng-lin Xu;Zhong Chen;Sunliang Cui
The voltage-gated sodium (Nav) channel is one of most important targets for treatment of epilepsy, and rufinamide is an approved third-generation anti-seizure drug as Nav1.1 channel blocker. Herein, by triazenylation of rufinamide, we reported the triazenyl triazoles as new Nav1.1 channel blocker for treatment of epilepsy. Through the electrophysiological activity assay, compound6aand6ewere found to modulate the inactivation voltage of Nav1.1 channel with shift of −10.07 mv and −11.28 mV, respectively. In the pentylenetetrazole (PTZ) mouse model,6aand6ereduced the seizure level, prolonged seizure latency and improved the survival rate of epileptic mice at an intragastric administration of 50 mg/kg dosage. In addition,6aalso exhibited promising effectiveness in the maximal electroshock (MES) mouse model and possessed moderate pharmacokinetic profiles. These results demonstrated that6awas a novel Nav1.1 channel blocker for treatment of epilepsy.
