Synthesis And Anticonvulsant Evaluation Of Some 4-Alkoxyl-3-Ethyl-4-H-1, 2, 4-Triazles

For finding safer and more potent anticonvulsant agents,A series of 4-alkoxyl-3-ethyl-4-H-1,2,4-triazoles derivatives(3a-s) was synthesized as open-chain analogues of 7-alkoxyl-4,5-dihydro[4,3-a]quinolines.Their structures were confirmed by ¹H-NMR,¹³C-NMR,IR and MS.Their anticonvulsant activities were evaluated by the maximal electroshock test(MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test(Tox).The results showed that most of them possessed the anticonvulsant activity,with ED₅₀ values 8.3 mg/kg and protective index(PI = TD₅₀/ED₅₀) value of 5.5,but compound 3r,3-ethyl-4-(4-octyloxyl)-4H-1,2,4-triazole,exhibited better PI value of 9.3,which was much greater than PI Value of the prototype drug phenytoin.For explanation of the possible mechanism of action,the compound 3r was tested,thiosemicarbazide test, 3-mercaptopropionic acid and strychnine test.As the sequence of the primary investigation,preserving the hexyloxy on the fourth position of phenyl ring,modified the substituted group of third position on triazole ring,we designed and synthesized a series of 3-substituted-4-(4-hexyloxyphenyl)-4H-1,2,4-triazole derivatives(4a-s).