3D-QSAR Studies on Chemical Features of 3-(benzo[d]oxazol-2-yl)pyridine-2-amines in the External Region of c-Met Active Site
3D-QSAR Studies on Chemical Features of 3-(benzo[d]oxazol-2-yl)pyridine-2-amines in the External Region of c-Met Active Site
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DOI：
10.5012/bkcs.2013.34.12.3553
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发表时间：
2013-12-20
影响因子：
1.7
通讯作者：
Chae, Chong Hak
中科院分区：
文献类型：
--
作者：
Lee, Joo Yun;Lee, Kwangho;Chae, Chong Hak
采用分子对接、比较分子场分析（CoMFA）和拓扑异构体CoMFA方法，对c-Met活性中心外区吡啶-2-胺类化合物的化学特征（ER化学特征）进行了三维定量构效关系（3D-QSAR）研究。CoMFA模型得到偏最小二乘（PLS）统计结果，交叉验证相关系数（q（2））为0.703，非交叉验证相关系数（r（2））为0.947，估计标准误差（SEE）为0.23;拓扑异构体CoMFA得到q（2）为0.803，r（2）为0.940，SEE为0.24。此外，应用测试集来验证模型的预测能力，其中CoMFA和拓扑异构体CoMFA模型的预测r（2）（r（pred）（2））分别为0.746和0.608。吡啶-2-胺的ER化学特征对抑制效力的每种贡献显示，对于两个核心部分，3-（苯并[d]恶唑-2-基）吡啶-2-胺和3-（1-（2，6-二氯-3-氟苯基）乙氧基）吡啶-2-胺，相关系数分别为0.670和0.913，具有相应的实验pIC（50）。
The three dimensional-quantitative structure activity relationship (3D-QSAR) studies on chemical features of pyridine-2-amines in the external region of c-Met active site (ER chemical features of pyridine-2-amines) were conducted by docking, comparative molecular field analysis (CoMFA), and topomer CoMFA methods. The CoMFA model obtained the partial least-squares (PLS) statistical results, cross-validated correlation coefficient (q(2)) of 0.703, non cross-validated correlation coefficient (r(2)) of 0.947 with standard error of estimate (SEE) of 0.23 and the topomer CoMFA obtained q(2) of 0.803, r(2) of 0.940, and SEE of 0.24. Further, the test set was applied to validate predictive abilities of models, where the predictive r(2) (r(pred)(2)) for CoMFA and topomer CoMFA models were 0.746 and 0.608, respectively. Each contribution of ER chemical features of pyridine-2-amines to the inhibitory potency showed correlation coefficients, r(2) of 0.670 and 0.913 for two core parts, 3(benzo[d]oxazol-2-yl)pyridine-2-amine and 3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy) pyridine-2-amine, respectively, with corresponding experimental pIC(50).