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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(ED_(50)=21.05mg/kg)。
Synthetic analogues of GABA are new areas for the development of novel anticonvulsants and antiepileptic drugs. Addition of α-aryl-α- (4-morpholino) acetonitrile formed by the reaction of aromatic aldehydes with morpholine and potassium cyanide allows 1,4-addition of α, β-unsaturated nitrile or ester to 1, 4-keto acid type compound. This material is condensed with hydrazine, and then aromatized to give 6-aryl-3 (2H) pyridazinone. The latter after chlorination. Condensation with GABA to prepare 3- (N-butyrolactam) -6-arylpyridazine derivatives of 3- (N-GABA) -6-aryl pyridazines and their intramolecular dehydration products. In this paper, 17 GABA derivatives of the above benzodiazepines were synthesized and preliminary tested their anti-shock (MES) activity. The most active is 3- (N-GABA) -6- (2 ’, 4’-dichlorophenyl) pyridazine (ED 50 = 21.05 mg / kg).