【摘要】 GABA的合成类似物是开发新型抗惊剂和抗癫痫药物的新领域。由芳香醛与吗啉、氰化钾反应形成的α-芳基-α-（4-吗啉）乙腈,可对α,β-不饱和腈或酯进行1,4-加成,生成1,4-酮酸型化合物。此物与肼缩合,再经芳构化即得6-芳基-3（2H）哒嗪酮。后者再经氯化后。与GABA缩合,制备3-（N-GABA）-6-芳基哒嗪类及其分子内脱水产物3-（N-丁内酰胺）-6-芳基哒嗪类化合物。本文应用此法合成了17个上述苯代哒嗪的GABA衍生物,并初步测验了它们的抗惊（MES）活性。活性最强的是3-（N-GABA）-6-（2′,4′-二氯苯基）哒嗪(ED₅₀=21.05mg/kg)。更多还原

【Abstract】 In recent years considerable emphasis has been placed on the hypothesis that enhancement of GABA transmission could be beneficial in some types of epilepsy. The α-（aryl）-4-morpholineacetonitrile obtained by the interaction of aryl aldehydes, morpholine and potassium cyanide, have been used to synthesize 3- （aroyl） -propionic acids and esters by 1,4- additions to acrylonitrile or acrylic ester. 3 - （ Aroyl ） propionic acids reacting with hydrazine can yield 6- aryl- 4, 5 - dihydro - 3（2H ） pyridazinones which are dehydrogenated by bromine （via bromination dehydrobromination） to give 6-aryl-3 （2H） pyridazinones. The latter compounds were converted into 3-（N-GABA） - 6 - （substitutedphenyl） pyridazines and 3 - （N- butyryllactamyl ） - 6-（substitutedphenyl） pyridazines by the chlorination （by means of phosphorus oxychloride） and then reaction with GABA. By this method seventeen 3-GABA derivatives of 6-（substituted - phenyl ） pyridazines were synthesized. The anticonvulsant activity （MES） of these compounds were also tested. 3 - （ N - GABA） - 6 - （ 2’, 4’- dichloro ） phenylpyridazine ; potent anticonvulsant (ED₅₀ = 21.05 mg/kg).更多还原