College of Pharmacy, Yanbian University, Jilin, China.
Arch Pharm (Weinheim). 2013 Feb;346(2):127-33. doi: 10.1002/ardp.201200201. Epub 2012 Dec 13.
A series of 4-(3-alkoxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-ones were synthesized using the appropriate synthetic route and evaluated experimentally in the maximal electroshock test; their neurotoxicities were evaluated by the rotarod neurotoxicity test. The structures of these compounds were confirmed by IR, MS, (1) H-NMR, and elementary analysis. All target compounds exhibited anticonvulsant activity to varying degrees in the maximal electroshock test. 4-(3-Benzyloxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one (4i) was the most promising compound with an ED(50) value of 30.5 mg/kg and a protective index (PI) of 18.63, showing a higher safety than the standard carbamazepine (PI=6.45). In addition, the potency of compound 4i against seizures induced by pentylenetetrazole and 3-mercaptopropionic acid suggested its broad-spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might be involved in its anticonvulsant activity.
一系列 4-(3-烷氧基-苯基)-2,4-二氢-[1,2,4]三唑-3-酮是通过适当的合成路线合成的，并在最大电休克试验中进行了实验评估；通过旋转棒神经毒性试验评估了它们的神经毒性。这些化合物的结构通过 IR、MS、(1)H-NMR 和元素分析得到证实。所有目标化合物在最大电休克试验中均表现出不同程度的抗惊厥活性。4-(3-苄氧基-苯基)-2,4-二氢-[1,2,4]三唑-3-酮（4i）是最有前途的化合物，ED（50）值为 30.5mg/kg，保护指数（PI）为 18.63，显示出比标准卡马西平更高的安全性（PI=6.45）。此外，化合物 4i 对戊四氮和 3-巯基丙酸诱导的癫痫发作的作用强度表明其具有广谱活性，其作用机制可能包括抑制电压门控离子通道和调节 GABA 能活性。
