Synthesis And Anticonvulsant Activities Of [1, 2, 4] Triazolo [4, 3-a] Quinolin-1(2H)-Ones

To Find compounds with better anticonvulsant activity and lower neurotoxicity,twelve 2-substituted-7-heptyloxy-4,5-dihydro-[1,2,4]-triazolo[4,3-a]quinolin-1(2H)-ones and four 2-substituted-7-benzyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1(2H)-ones derivatives were synthesized using 6-hydroxy-3,4-dihydro-2(1H)-quinolone as a starting material,and their anticonvulsant activities were evaluated by the maximal electroshock test(MES) and the subcutaneous pentylenetetrazole test(sc-PTZ) and their neurotoxicities were measured by the rotarod neurotoxicity test(Tox).The results showed that 2-propionyl-7-(heptyloxy)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1(2 H)-one(4b) was the most potent with ED₅₀ values of 8.18 mg/kg and the protective index(PI = TD₅₀/ED₅₀) values of 39 in the MES.The PI values of 4b was better than that of the marketed drugs phenytoin,carbamazepin, phenobarbital and valproate which have PI values in the range of 1.6-8.1 in the MES test.It also better than the lead compound 3.It was found that [1,2,4]triazole[4,3-a]quinolin-1-ones possess the potent of being explored to be a new anticonvulsant agent.