Design, synthesis of 8-alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-ones with anticonvulsant activity

A new series of 8-alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one derivatives were synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The results showed that 8-heptyloxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one 5t was the most potent with median effective dose (ED50) value or 11.4 mg/kg, median toxicity dose (TD50) of 114.1 mg/kg, providing a protective index (PI = TD50/ED50) value of 10.0, which is much greater than the PI of the prototype drug carbamazepine (PI=6.4). To explain the possible mechanism of anticonvulsant activity, the compound 5t was tested in chemically induced seizures. (C) 2008 Elsevier Masson SAS. All rights reserved.