1—取代苄基吡唑烷酮类的合成及其抗惊作用的研究  

SYNTHESIS OF 1-SUBSTITUTED BENZYL-PYRAZOLIDONES AND THEIR ANTICONVULSANT ACTIVITY

作　　者：凌仰之[1] 李莉[2] 钟三保[1] 雷小平[1] 

机构地区：[1]北京医科大学药化教研室,北京100083 [2]北京医科大学

出　　处：《中国药物化学杂志》1991年第1期1-6,21,共7页Chinese Journal of Medicinal Chemistry

基　　金：中国自然科学基金;国家医药管理局资助课题

摘　　要：按Topliss法设计并合成了八个1-取代苄基-3-吡唑烷酮衍生物(7b-i),发现其抗惊活性与取代基的σ+π值有关,其中以1-对三氟甲基苄基—吡唑烷酮-3(7i)活性最强。改进了合成1-取代吡唑烷酮的方法,先由丙烯腈与肼直接一步合成3-亚氨物(2),再与醛缩合并用NaBH_4还原,实现了“一勺烩”,最后再水解。从而简化了步骤,提高了收率。By the Topliss^1 method, eight 1-substituted benzyl-pyrazolidon e-3 derivatives (7b-i) were designed and synthesized. Pharmacological tests showed that their anticonvulsant activity was related to their^1σ+π'parameter of the substituents.1p-tri-fluoromethyl benzyl-pyrazolidone-3 was the most potent one,ED5o=67.8mg/kg anti MES Test. From acrylonitrile, 3-amino-pyrazolidine (2) was synthesized directly, and then condensed with aldehyde, reduced by sodium borohydride within a single procedure, and finally hydrolyzed to give(7).

关 键 词：1-取代-吡唑烷酮类 Topliss设计法 抗惊作用 

分 类 号：R914[医药卫生—药物化学]