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化学学报
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化学学报 ›› 2006, Vol. 64 ›› Issue (11): 1097-1105.    下一篇

研究论文

2-嘧啶氧基-N-芳基苄胺类化合物的ALS抑制活性的QSAR研究

冯骁1，姚建华*,2，吕龙*,1，唐庆红1，范波涛3   

  1. (1中国科学院上海有机化学研究所有机氟化学重点实验室 上海 200032)
    (2中国科学院上海有机化学研究所计算机化学和化学信息学研究室 上海 200032)
    (3法国巴黎第七大学化学系ITODYS 巴黎 75005 法国)
  • 投稿日期:2005-07-07 修回日期:2006-02-07 发布日期:2006-06-15
  • 通讯作者: 姚建华

QSAR Study for Inhibiting Activity of 2-(4,6-Dimethoxy-pyrimidin-2-yloxy)-N-het/aryl-benzylamine Derivatives Against Acetolactate Synthase

FENG Xiao1, YAO Jian-Hua*,2, LÜ Long*,1, TANG Qing-Hong1, FAN Bo-Tao3   

  1. (1 Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032)
    (2 Department of Computer Chemistry & Chemoinformatics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032)
    (3 ITODYS, Department of Chemistry, University of Paris 7, Paris 75005, France)
  • Received:2005-07-07 Revised:2006-02-07 Published:2006-06-15
  • Contact: YAO Jian-Hua

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乙酰乳酸合成酶(ALS)或乙酰羟酸合成酶(AHAS)存在于植物的生长过程中, 很多此类酶的抑制剂实际上作为除草剂被广泛用于农业生产中. 生物活性测试结果表明, 2-嘧啶氧基-N-芳基苄胺类化合物对ALS具有一定的抑制活性. 在此基础上, 我们用两种三维定量构效关系(3D-QSAR)研究方法: 比较分子立场分析(CoMFA)和比较分子相似性指数分析(CoMSIA), 对该类化合物进行了3D-QSAR研究, 并建立了相关的预测模型. 其中, CoMFA模型的交叉验证相关系数(rcv2)为0.801, 非交叉验证相关系数(r2)为0.947, 标准偏差(s)为0.136, F值为133.371. CoMSIA模型的rcv2为0.744, r2为0.883, s为0.202, F值为56.472. 计算结果表明, 2-嘧啶氧基-N-芳基苄胺类化合物与ALS抑制活性有一定的相关性. 获得的CoMFA和CoMSIA模型, 将应用于指导该类化合物的设计.

关键词: 乙酰乳酸合成酶, 2-嘧啶氧基-N-芳基苄胺类化合物, 三维定量构效关系, 抑制活性

According to the result of biological experiments, 2-(4,6-dimethoxy-pyrimidin-2-yloxy)-N-het/ aryl-benzylamine derivatives were found to have the inhibiting activity of acetolactate synthase (ALS), and the relationship between these compounds and their activity was studied by 3D-QSAR: CoMFA and CoMSIA. For CoMFA model, crossvalidated correlation coefficient rcv2 is 0.801, the proportion of the original variance r2 is 0.947, standard error is 0.136 and the ratio of r2 to 1.0-r2 is 133.371. For CoMSIA model, they are 0.744, 0.883, 0.202 and 56.472 respectively. The results indicate that there is a correlation between 2-(4,6-dimethoxy-pyrimidin-2-yloxy)-N-het/aryl-benzylamine derivatives and inhibiting activity of ALS. The CoMFA and CoMSIA models will be useful for molecular design for this kind of compounds.

Key words: acetolactate synthase (ALS), 2-(4,6-dimethoxy-pyrimidin-2-yloxy)-N-het/aryl-benzylamine derivatives, three-dimension quantitative structure-activity relationship (3D-QSAR), inhibiting activity