.7 - Substituted -4,5 - Dihydro - [1,2,4] Triazolo [4,3-a] Quinoline Design, Synthesis, And The Role Of Anticonvulsant Activity,

For finding safer and more potent anticonvulsant agents, 31 derivatives, in which 26 were unreported in previous literatures, were designed depended on 7-benzyoxyl -4,5-dihydro -[1,2,4] triazole [4,3-a] quinolines as our leading compound, according the classic optimization methods. Their structures were confirmed by¹H-NMR, ¹³C-NMR, IR and MS. The anticonvulsant activity of them was evaluated by the maximal electroshock test (MES), the subcutaneous pentyleneterazol (sc-PTZ) and the rotarod neurotoxicity test (Tox). The results showed that most of them possessed the anticonvulsant activity, with ED50 values 11.8 mg/kg and 6.7mg/kg in MES test and PTZ test, respectively, 7-(4-flurobenzyloxyl)-4,5-dihydro-[1,2,4]triazole [4,3-a]quinoline 4k was found to be the most potent in the synthesized compounds, which was more potent than that of Phenobarbital. With ED₅₀ values 5.0 mg/kg in PTZ test and TD50 102 mg/kg in Tox test, respectively, 7-(3-brominebenzylamine)-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline 5o was the safest compound. Its PI (TD50/ED50) value was more than 20 in corresponding test, of which was much more that of the general clinical drugs. The rationality of the electro isotster optimization method used in this series compounds was revealed by possessing anticonvulsant activity of the electro isosters(5a-5o) of our leading compound.leading compound compound 4k compound So...