8-取代-6-苯基-[1,2,4]三唑并[4,3-b]哒嗪类化合物的合成及抗癫痫活性研究

目的]设计合成一系列8-烷氧基-6-苯基-1,2,4]三唑并4,3-b]哒嗪类化合物(3a³h)和8-苯氧基-6-苯基-1,2,4]三唑并4,3-b]哒嗪类化合物(5a3h)和8-苯氧基-6-苯基-1,2,4]三唑并4,3-b]哒嗪类化合物(5a⁵j),并评价其抗惊厥活性.方法]以4-氨基-1,2,4]-三唑为起始原料,在160℃条件下与苯甲酰乙酸乙酯熔融环合,而后经过氯代、烷基化等反应合成一系列三唑并4,3-b]哒嗪类衍生物.应用最大电惊厥实验测定目标化合物的抗惊厥活性.结果]合成了18个未见文献报道的新型化合物,所有化合物的化学结构均经IR,1 H-NMR和MS方法确证.部分所合成化合物在100mg/kg时表现出一定的抗惊厥活性,其中化合物3c(8-正丁氧基-6-苯基-1,2,4]三唑并4,3-b]哒嗪)的抗惊厥活性最强.

Synthesis and anticonvulsant activities of 8-substituted-6-phenyl-[1,2,4]triazolo[4,3-b]pyridazine

OBJECTIVE To design and synthesize the 8-alkoxy-6-phenyl-1,2,4]triazolo4,3-b]pyridazine derivatives（3a-3h）and 8-phenoxy-6-phenyl-l,2,4]triazolo4,3-b]pyridazine compounds（5a-5j）,and evaluate their anticonvulsant activities.METHODS6-Phenyl-1,2,4]triazolo4,3-b]pyridazine derivatives were synthesized via the reaction of ethyl benzoylacetate with 1,2,4-triazol-4-amine in the absence of solvent at 160℃,and then got the aim compounds by alkylate etc.Their anticonvulsant activities were measured by maximal electroshock（MES）test.RESULTSA total of 18 pyridazine series of derivatives are novel compounds that have not been reported.Their structures were characterized by IR,^1 HNMR,^13C-NMR and MS.Their anticonvulsant activities were respectively evaluated by the MES.Some of them displayed promising activities at 100mg/kg,in witch 3c（8-butoxy-6-phenyl-1,2,4]triazolo4,3-b]pyridazine）has the best acticonvulsant activities.