1,3-二氮杂螺[4,5/4]癸/壬-1-烯-4-酮类衍生物的定量构效关系  

Study on Quantitative Structure-activity Relationship of 1,3-Diazaspiro[4,5/4] dec/non-1-en-4-one Derivatives

作　　者：刘念[1] 魏庆莉[1] 丁彩凤[1] 张书圣[1] 

机构地区：[1]青岛科技大学化学与分子工程学院,山东青岛266042

出　　处：《青岛科技大学学报（自然科学版）》2005年第6期493-496,共4页Journal of Qingdao University of Science and Technology:Natural Science Edition

基　　金：青岛科技大学博士基金资助项目

摘　　要：采用Gaussian98量子化学计算软件,运用半经验AM1方法在3-21G基组水平上优化了14个1,3-二氮杂螺[4,5/4]癸/壬-1-烯-4-酮的联苯磺酰胺类衍生物的几何构型,并根据Hansch-Fujita方法对该类化合物进行了系统的定量构效关系(QSAR)研究。建立了联苯磺酰胺类衍生物抑制AⅡ诱导活性IC50与LUMO轨道能量本征值ELUMO、疏水参数clogP和分子摩尔折射参数CMR的相关方程,方程复相关系数r=0.923 3。研究结果表明,化合物LUMO轨道能量越低越容易接受电子,其生物活性越高;R2位引入正电性基团有利于提高化合物生物活性;化合物疏水效应越小,越易与受体结合,其生物活性越高,当杂螺环上n=1时化合物的疏水参数偏小,其生物活性相应较高;化合物极化效应越好,分子越容易极化,则化合物的生物活性越高。The geometry structures of 1,3-diazaspiro[4, 5/4] dec/non-l-en-4-one derivatives were optimized using Gaussian98 software and AM1 method on 3-21 G basis sets. The quantitative structure-activity relationship（QSAR） of the compounds was systematically investigated based on Hasch-Fujita approach. A correlative equation between the IC50 of antagonistic activity and ELUOM, clogP and CMR was well established. The correlation coefficient r is 0. 923 3. The results showed that the introduction of electron- withdrawing group onto the R^2-position would be favorable to the bioactivity of the compounds. ClogP was influenced by the number of carbon on the spiro. Reducing of clogP and building up the polarization of compounds would be favorable to the bioactivity.

关 键 词：1 3-二氮杂螺[4 5/4]癸/壬-1-烯-4-酮 定量构效关系 半经验 

分 类 号：O621[理学—有机化学]