物理化学学报 >> 2008, Vol. 24 >> Issue (10): 1859-1863.doi: 10.3866/PKU.WHXB20081020

研究论文 上一篇    下一篇

苯并嗪酮衍生物的3D-QSAR分析

蒋玉仁; 秦伟   

  1. 中南大学化学化工学院, 长沙 410083
  • 收稿日期:2008-05-19 修回日期:2008-06-08 发布日期:2008-10-08
  • 通讯作者: 蒋玉仁 E-mail:jiangyr@mail.csu.edu.cn

3D-QSAR Analysis on Benzoxazinone Derivatives

JIANG Yu-Ren; QIN Wei   

  1. College of Chemistry & Chemical Engineering, Central South University, Changsha 410083, P. R. China
  • Received:2008-05-19 Revised:2008-06-08 Published:2008-10-08
  • Contact: JIANG Yu-Ren E-mail:jiangyr@mail.csu.edu.cn

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摘要： 苯并嗪酮衍生物是近年来发现的一类抗血小板聚集化合物, 在前人研究的基础上利用比较分子场分析(CoMFA)和比较分子相似性指数分析(CoMSIA)对23个苯并嗪酮衍生物进行了三维定量构效关系(3D-QSAR)研究. 其中CoMFA模型交叉验证系数Q2=0.703, 回归系数R2=0.994, 计算值与实验值的平均方差SEE=0.053, 统计方差比F=184.773; CoMSIA模型Q2=0.847, R2=0.992, SEE=0.058, F=171.670. 两种方法得到的模型都具有较好的预测能力. 结果表明, 标题化合物中8-位取代基R1静电效应起主要作用; 2-位取代基R2立体效应占主导作用, 但官能团大小要适中. 根据研究结果设计了六种活性较高的化合物.

关键词: 苯并嗪酮衍生物, 三维定量构效关系, 比较分子力场分析, 比较分子相似性指数分析

Abstract: Benzoxazinone derivatives have recently been reported as a type of compounds with potential antiplatelet activity. On the basis of published papers, comparative molecular field analysis (CoMFA) and comparative molecular similiarity indices analysis (CoMSIA) were used to gain insight into the three dimensional quantitative structure activity relationships (3D-QSAR) of benzoxazinone derivatives. The coefficients of cross-validation Q2 and non cross-validation R2 for CoMFA model established in this study were 0.703 and 0.994, respectively, and for CoMSIA model were 0.847 and 0.992. The results indicated that the two models had good predictability. The 3D contour maps suggested that the electrostatic effect of 8-substituted group R1 and the steric effect in the 2-substituted group R2 with moderate volume played major roles. Six compounds with new activities were designed on the basis of these conclusions.

Key words: Benzoxazinone derivatives, 3D-QSAR, CoMFA, CoMSIA

MSC2000: 

  • O641