Synthesis And Activity Of Quinoline And Heterocyclic Compounds

To Find compounds with better anticonvulsant activity and lower neurotoxicity, twelve 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-α]quino-line-1-one derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material, and ten novel beterocycle [a]quinoline derivatives was synthesized starting from 6-hydroxy-3,4-dihydro-2(1H)-quinolone. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ) and their neurotoxicity were measured by the rotarod neurotoxicity test (Tox).The tests showed that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3-α]quinoline-1-one (4e) was the most potent with ED₅₀ values of 17.17 mg/kg and 24.55 mg/kg and the protective index (PI=TD₅₀/ED₅₀) values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many folds better than that of the marketed drugs phenytoin, carbamazepin, phenobarbital and valproate which had PI values in the range of 1.6-8.1 in the MES test. It was found that [1,2,4] triazole [4,3-α] quinoline-1-one compounds possess the potent of being explored to be a new anticonvulsant agent.