刘晶,李燕,杨银凤,张述伟,杨凌,闫玉莲.5-HT 6受体拮抗剂三维定量构效关系研究[J].,2012,(3):327-332 |
5-HT 6受体拮抗剂三维定量构效关系研究 |
Study of 3D-QSAR of 5-HT 6 receptor antagonists |
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DOI:10.7511/dllgxb201203003 |
中文关键词: 三维定量构效关系 5-HT 6 拮抗剂 比较分子场分析 比较分子相似性指数分析 |
英文关键词: 3D-QSAR 5-HT 6 antagonist CoMFA CoMSIA |
基金项目:大连理工大学青年教师培养基金资助项目(1000893231). |
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中文摘要: |
为指导合成高效的5-HT 6受体拮抗剂,采用比较分子场分析(CoMFA)和比较相似性指数分析(CoMSIA)对143个5-HT 6受体拮抗剂数据进行了三维定量构效关系(3D-QSAR)研究,分别得到了具有良好可靠性和预测能力的CoMFA( Q 2=0.513, R 2 ncv =0.864, R 2 pre = 0.731) 和CoMSIA模型( Q 2=0.515, R 2 ncv =0.844, R 2 pre =0.777).由模型的等势线图分析,可得如下结论:大体积及/或电负性较大的 R 2取代基、疏水性 R 3和疏水性苯环 R 1位取代基、可作氢键受体的 R 2取代基、可作氢键供体的 R 3取代基有助于增大活性.这些结论能够更好地帮助理解5-HT 6受体拮抗剂的抑制机理,并为今后的药物设计与合成提供新思路. |
英文摘要: |
Based on a data set of 143 5-HT 6 antagonists, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out to aid in the design of 5-HT 6 antagonists with potent activity to build 3-dimensional quantitative structure-activity relationship (3D-QSAR) models. The results show that both the optimal CoMFA ( Q 2= 0.513, R 2 ncv =0.864, R 2 pre =0.731) and CoMSIA ( Q 2=0.515, R 2 ncv =0.844, R 2 pre =0.777) models have good reliabilities and predictive abilities. Additionally, from the analysis of the contour maps, it can be concluded that bulky R 2 substituent with/or without negatively charges, hydrophobic groups both in R 3 and R 1 substituent at the benzene ring, HB acceptor substituent in R 2 and HB donor substituent in R 3 will benefit the activity. All the conclusions can supply useful information for better understanding of the mechanism of 5-HT 6 antagonism and are also helpful in providing new clues for drug design and synthesis. |
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