5-取代苯基,1-氢及1-正丙基吡唑烷酮-3化合物抗惊作用QASR的研究  

QSAR STUDIES ON THE ANTICONVULSANT ACTIVITY OF 5-SUBSTITUTEDPHENYL-1-HYDRO-AND 1-PROPYL - 3- PYRAZOLIDINONES

作　　者：雷小平[1] 栾燕[1] 凌仰之[1] 李仁利[1] 裴印权[1] 

机构地区：[1]北京医科大学,北京100083

出　　处：《药学学报》1990年第9期684-688,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金;国家医药局资助课题

摘　　要：研究了5-取代苯基吡唑烷酮-3衍生物中苯基取代基的变化对抗惊活性的影响。按照Topliss改进法设计并合成了。1-氢及1-正丙基取代的化合物各六个,找到了活性较强的化合物,为5-(对氟苯基)-1-丙基吡唑烷酮-3,其ED_(50)为14.7mg/kg。经QSAR研究,发现疏水参数∑π对活性影响较大,苯上取代基的立体参数B_4和电性参数Ⅰ×10~2可以改进相关系数r。方程说明5-位苯上引入体积小的吸电子基团可使抗惊活性提高。The chemical structure and anticonvulsant activity relationship of some 5 - substituted phenyl - 3 - pyrazolidinone derivatives were studied Six pairs (1 - hydro and 1 - propyl substituted) of compounds were designed and synthesized according to the Topliss improved method, and a compound with the highest anticonvulsant activity was found, i. e. 5 - (4-fluorophenyl) - 1 - propyl - 3 - pyrazolidinone, ED_(50) 14.7 mg/kg (MES Test). QSAR analysis showed that the hydrophobic constant ∑ π greatly influenced their anticonvulsant activity, and the steric parameter (B_4) and electronic parameter (Ⅰ×10~2) of the substitutions on the phenyl ring can improve the correlation coefficient (r). Smaller steric volume and more powerful electron withdrawing effect of the substitution on the 5-phenyl ring increased the anticonvulsant activity.

关 键 词：吡唑烷酮 抗惊活性 定量构效关系 

分 类 号：R965.1[医药卫生—药理学]