Based on the potent antidepressant and anticonvulsant activities of the triazole-containing quinolinones reported in our previous work, a series of ring-opened derivatives of them were designed, synthesized in this work. Their antidepressant and anticonvulsant activities were screened using the forced swimming test (FST) and the maximal electroshock seizure test (MES), respectively. The results showed that compounds 4a, 5a, 6c-6e, 6g-6i, and 7 led to significant reductions in the accumulated immobility time in the FST at a dose of 50 mg/kg. Especially compound 7 exhibited higher levels of efficacy than the reference standard fluoxetine in the FST and the tail suspension test. The results of an open field test excluded the possibility of central nervous stimulation of 7, which further confirmed its antidepressant effect. Meanwhile, compounds 6a-6i and 7 showed different degrees of anticonvulsant activity in mice at the doses range from 300 to 30 mg/kg in the MES. Among them, compounds 6e and 7 displayed the ED₅₀ of 38.5 and 32.7 mg/kg in the MES, and TD₅₀ of 254.6 and 245.5 mg/kg, respectively. No one showed neurotoxicity at the dose of 100 mg/kg. The preliminary investigation forward to their mechanism indicated that regulation of GABAergic system might contribute to their anticonvulsive and anti-depressive action.

基于我们先前工作中报道的含三唑喹啉酮类化合物的有效抗抑郁和抗惊厥活性，本工作设计并合成了它们的一系列开环衍生物。分别使用强迫游泳试验（FST）和最大电休克癫痫试验（MES）来筛选它们的抗抑郁和抗惊厥活性。结果表明，化合物4a、5a、6c-6e、6g-6i和7在 50mg/kg 剂量下导致 FST 中累积不动时间显着减少。特别是化合物7在 FST 和悬尾试验中表现出比参考标准氟西汀更高的功效水平。旷场试验结果排除了7 的中枢神经刺激作用，进一步证实了其抗抑郁作用。同时，化合物6a-6i和7在 MES 中剂量范围为 300 至 30 mg/kg 时在小鼠中显示出不同程度的抗惊厥活性。其中，化合物6e和7在MES中的ED _50分别为38.5和32.7 mg/kg，TD ₅₀分别为 254.6 和 245.5 mg/kg。没有人在 100 mg/kg 的剂量下表现出神经毒性。对其机制的初步研究表明，GABAergic 系统的调节可能有助于其抗惊厥和抗抑郁作用。