目的设计合成一系列1,2,4-三唑并[4,3-a]喹啉衍生物,并评价其抗惊厥活性和神经毒性。方法以4-羟基喹啉-2(1H)酮为起始原料,经烷基化、氯代、肼代、环合等反应合成1,2,4-三唑并[4,3-a]喹啉衍生物。通过最大电惊厥实验(MES)和旋转棒法(Rotarod),分别测定目标化合物的抗惊厥活性和神经毒性。结果合成了12个新化合物,其结构经1H-NMR、EI-MS和IR谱确证。结论药理学实验结果表明,部分化合物在不同剂量下显示出抗惊厥活性,其中,5-苄氧基-1-甲基-[1,2,4]三唑并[4,3-a]喹啉(10b)的活性最强,其半数有效量ED50值为18.0mg.kg-1,保护指数PI为7.9,虽然该化合物的活性低于阳性对照药卡马西平,但其保护指数优于卡马西平(PI=6.4),有进一步研究的价值。 Aim To design and synthesize a series of 1,2,4-triazolo [4,3-a] quinoline derivatives and evaluate their anticonvulsant activity and neurotoxicity. Methods 1,2,4-Triazolo [4,3-a] pyrazole was synthesized by the reaction of 4-hydroxyquinolin-2 (1H) Quinoline derivatives. The anticonvulsant activity and neurotoxicity of the target compounds were respectively determined by maximum electroconvulsive test (MES) and Rotarod method. Results Twelve novel compounds were synthesized and their structures were confirmed by 1H-NMR, EI-MS and IR. Conclusion The results of pharmacological experiments showed that some of the compounds showed anticonvulsant activity at different doses. Among them, 5-benzyloxy-1-methyl- [1,2,4] triazolo [4,3-a] (10b) showed the strongest activity with a half-value effective amount of ED50 of 18.0 mg.kg-1 and a protective index of PI of 7.9. Although the activity of this compound was lower than that of the positive control carbamazepine, the protection index was superior to that of the card Macassin (PI = 6.4), with further research value.