3D-QSAR studies on fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors by CoMFA and CoMSIA
3D-QSAR studies on fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors by CoMFA and CoMSIA
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CoMFA 和 CoMSIA 对氟吡咯烷酰胺作为二肽基肽酶 IV 抑制剂的 3D-QSAR 研究
DOI：
10.1007/s00894-007-0221-8
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发表时间：
2007-07
影响因子：
2.2
通讯作者：
Tang, Yun
中科院分区：
文献类型：
--
作者：
Zeng, Juan;Jiang, Hualiang;Liu, Guixia;Tang, Yun
采用CoMFA和CoMSIA方法对一系列氟代吡咯烷酰胺类二肽基肽酶IV（DP-IV）抑制剂进行了三维定量构效关系（3D-QSAR）分析。利用GOLD软件将所选配体对接到DP-IV三维模型的结合位点，得到了DP-IV与抑制剂之间可能的相互作用模型。基于这些氟代吡咯烷酰胺的结合构象及其在DP-IV结合口袋内的排列，通过CoMFA和CoMSIA分析建立了预测性3D-QSAR模型，CoMFA的常规r2和交叉验证系数（）分别为0.982和0.555，CoMSIA的r2和交叉验证系数（）分别为0.953和0.613。这些模型的预测能力通过测试集中的六种化合物进行了验证。基于结构的研究和最终的3D-QSAR结果为设计新的有效抑制剂提供了指导。
Three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses using CoMFA and CoMSIA methods were conducted on a series of fluoropyrrolidine amides as dipeptidyl peptidase IV (DP-IV) inhibitors. The selected ligands were docked into the binding site of the 3D model of DP-IV using the GOLD software, and the possible interaction models between DP-IV and the inhibitors were obtained. Based on the binding conformations of these fluoropyrrolidine amides and their alignment inside the binding pocket of DP-IV, predictive 3D-QSAR models were established by CoMFA and CoMSIA analyses, which had conventionalr2and cross-validated coefficient values () up to 0.982 and 0.555 for CoMFA and 0.953 and 0.613 for CoMSIA, respectively. The predictive ability of these models was validated by six compounds that were in the testing set. Structure-based investigations and the final 3D-QSAR results provide the guide for designing new potent inhibitors.
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影响因子：
7.3
作者：
E. B. Villhauer;J. Brinkman;Goli B Naderi;B. Dunning;B. L. Mangold;M. Mone;M. E. Russell;S. Weldon;T. Hughes
通讯作者：
E. B. Villhauer;J. Brinkman;Goli B Naderi;B. Dunning;B. L. Mangold;M. Mone;M. E. Russell;S. Weldon;T. Hughes
影响因子：
7.3
作者：
Böhm, M;Stürzebecher, J;Klebe, G
通讯作者：
Klebe, G
DOI：
10.1016/0263-7855(93)80051-r
发表时间：
1993-12
期刊：
Journal of Molecular Graphics
影响因子：
--
作者：
W. Brandt;T. Lehmann;A. Baith;S. Fittkau
通讯作者：
W. Brandt;T. Lehmann;A. Baith;S. Fittkau
DOI：
10.1038/nsb882
发表时间：
2003-01-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Rasmussen, HB;Branner, S;Wagtmann, N
通讯作者：
Wagtmann, N
DOI：
10.3109/10409239309082572
发表时间：
1993
影响因子：
6.5
作者：
A. Yaron;F. Naider
通讯作者：
A. Yaron;F. Naider