4-[(4-氯苯基)(5-氟-2-羟基苯基)亚甲氨基]丁酸酯类的合成及其抗惊厥活性

Synthesis of 4-[(4-chlorophenyl) (5-fluoro-2-hydroxyphenyl) methylene amino]butyrates and Its Anticonvulsant Activity

作者设计并合成了8个γ-氨基丁酸(GABA)的衍生物(Ⅳ_(a-b)),使GABA的酯通过亚胺键,连接在一个易于通过血脑屏障的亲脂性载体上。合成的8个标题化合物,均用NIH提出的抗癫痫药物开发程序进行评价,结果化合物Ⅳ_b和Ⅳ_f表现出有效的抗惊厥活性。

It is known that γ-aminobutyric acid(GABA) plays an important role in thepathophysiology of epilepsy.Under physio-logical conditions it is very difficult forGABA to cross the blood-brain barrier. Itis likely that the esters of GABA, Whicheasily enter the brain, will have usefultherapeutic properties. With this in mind,wehave designed and synthesized 8 deriva-tives (Ⅳ_a to Ⅳ_h) of γ-aminobutyric acidwith an imine to link a lipophilic carrierin order to facilitate the passage of γ-ami-nobutyric acid to cross the blood-brainbarrier. All the eight synthesized title com-pounds were evaluated as anticonvulsantsinmice via the Antiepileptic Drug Develop-ment Program of NIH.The compounds Ⅳ_band Ⅳ_f showed anticonvulsant activity.