7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉和喹啉-1(2H)-酮衍生物的合成及抗惊厥活性

合成了7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉(3a～3g)和7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹表明啉-1(2H)-酮(4a～4g)类衍生物. 以最大电惊厥法和戊四唑法测定了抗惊厥活性, 以旋转棒法测定了神经毒性. 结果表明, 化合物7-(4-氟苯氧基)-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉-1(2H)-酮(4c)显示最强的抗惊厥作用和低的神经毒性, 其抗电惊厥ED₅₀为6.8 mg/kg, 神经毒性TD₅₀为88.0 mg/kg, 保护指数PI为12.9, 明显优于对照药苯妥英钠.

Synthesis and Anticonvulsant Activity Study of 7-SubstitutedPhenoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines andQuinoline-1(2H)-ones

A series of 7-(substituted phenoxyl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines and 7-(substi-tuted phenoxyl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-ones were synthesized. The convulsant effect and neurotoxicity of the compound were determined with maximal electroshock test (MES), penty-lenetetrazol (PTZ) method and rotarod test intraperitoneally in mice. 7-(4-Fluorophenyloxy)-4,5-dihy-dro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-one (4c) was the most active and also has the lowest toxicity. In the anti-MES potency test, 4c showed a medial effective dose (ED50) of 6.8 mg/kg, a medial toxicity dose (TD50) of 88.0 mg/kg, and the protective index (PI) of 12.9. The PI value of compound 4c was better than that of the marketed drug phenytoin.