6-[4-(取代哌嗪基)苯基]-4,5-二氢-3(2H)-哒嗪酮类化合物的三维定量构效关系研究  

3 D-QSAR Study of a Series of 6-[4-Substituted-piperazinyl) phenyl]-4,5-Dihydro-3(2H)-Pyridazinones

作　　者：张俊[1] 孙青 徐建明[1] 薛云云[1] 曾娟[2] 黄晓瑾[3] 吴秋业[1] 

机构地区：[1]第二军医大学药学院,上海200433 [2]华东理工大学药学院,上海200237 [3]中国人民解放军第85医院药剂科,上海200052

出　　处：《药学实践杂志》2008年第3期178-181,共4页Journal of Pharmaceutical Practice

基　　金：上海市长宁区科委基金(20054Y17001)资助项目

摘　　要：本文采用比较分子力场分析法(CoMFA),系统研究了自行合成的34个6-[4-(取代哌嗪基)苯基]-4,5-二氢-3(2H)-哒嗪酮类化合物和参比化合物CCI-17810的三维定量构效关系。所建立CoMFA模型的交叉相关系数q2值为0.663,具有较强的预测能力。利用CoMFA模型的三维等值线图直观地解释了化合物的构效关系,阐明了化合物结构中哌嗪末端N原子上不同取代基对抗血小板聚集活性的影响,为进一步结构优化提供了重要信息。Three dimensional structure-activity relationship （3 D-QSAR） has been studied on a series of 6-[ 4-Substituted-piperazi- nyl） phenyl] -4,5-Dihydm-3 （ 2H ） -Pyridazinones by using. Using comparative molecular field analysis （CoMFA）. The resulting CoMFA model had a cross validated coeffiecient q^2 of 0. 663 respectively, which showed a strong predictive ability. The 3D contour maps of CoMFA provided a smooth and interpretable explanation of the structure-antiplatelet aggregation activity relationship for the compounds. The analysis of the 3D contour plots permitted interesting conclusions about the effects of different substituent groups at the position of the N atom on the terminal of piperazidine group on the antiplatelet aggregation activity, which will guide the design of novel antiplatelet aggregation compounds with relatively high activity.

关 键 词：哒嗪酮 抗血小板聚集 比较分子力场分析法 三维定量构效关系 

分 类 号：R914.5[医药卫生—药物化学]