The synthesis and anticonvulsant activity of 1-substituted-7-methoxy-1,2,4,-triazolo [4, 3-a] quinoline

Abstract

A new series of 1-substituted-7-methoxy-5-phenyl-1,2,4-triazolo[4,3-a]quinolines were synthesized using ethyl-3-oxo-3-phenylpropanoate and 4-methoxybenzenamine as the starting material. Their anticonvulsant activity was evaluated by the maximal electroshock (MES) test and 7-methoxy-5-phenyl-1,2,4-triazolo[4,3-a]quinoline (4a) was identified as the most potent compound, with an $ED_{50}$ value of 9.2 mg $kg^{−1}$, which is comparable to the reference drug phenytoin ($ED_{50}$ = 9.9 mg $kg^{−1}$). To explore the possible mechanism of its anticonvulsant activity, compound 4a was tested with the rotarod neurotoxicity test, pentylenetetrazole (sc-PTZ) test, and isoniazid test. Compound 4a had a higher protective index (PI = $TD_{50}/ED_{50}$) value (16.6) than phenytoin (PI = 7.0), and it antagonized pentylenetetrazole- and isoniazid-induced seizures with an ED50 of 21.1 mg $kg^{−1}$ and 83.3 mg $kg^{−1}$, respectively.