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

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.