College of Pharmacy, Yanbian University, No. 977 Park Road, Yanji 133002, Jilin, China.
Arch Pharm Res. 2013 Jan;36(1):32-40. doi: 10.1007/s12272-013-0006-9.
Two series of 8-alkoxy-5-(4H-1,2,4-triazol-4-yl)quinolines and 8-alkoxy-5-(2H-1,2,4-triazol-3-one-4-yl)quinolines were synthesized. The anticonvulsant activity of these compounds was evaluated with maximal electroshock seizure test and rotarod test. Among the synthesized compounds, 8-octoxy-5-(4H-1,2,4-triazol-4-yl)quinoline (4g) was the most active compound with ED(50) of 8.80 mg/kg, TD(50) of 176.03 mg/kg and protective index of 20.0. Its neurotoxicity was lower than all other synthesized compounds and also markedly lower than that of the reference drug carbamazepine. In addition, the potency of compound 4g against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline suggested its broad spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might involve in its anticonvulsant activity.
合成了两个系列的 8-烷氧基-5-(4H-1,2,4-三唑-4-基)喹啉和 8-烷氧基-5-(2H-1,2,4-三唑-3-酮-4-基)喹啉。用最大电休克惊厥试验和旋转棒试验评价这些化合物的抗惊厥活性。在所合成的化合物中，8-辛氧基-5-(4H-1,2,4-三唑-4-基)喹啉（4g）是最活性化合物，ED（50）为 8.80 mg/kg，TD（50）为 176.03 mg/kg，保护指数为 20.0。其神经毒性低于所有其他合成化合物，也明显低于参考药物卡马西平。此外，化合物 4g 对戊四氮、3-巯基丙酸和印防己毒素诱发的惊厥的作用强度提示其具有广谱活性，其作用机制包括抑制电压门控离子通道和调节 GABA 能活性，可能与其抗惊厥活性有关。
