吲哚-2-酮类化合物作为PDGF-Rβ酶抑制剂的3D-QSAR研究

Study on indol-2-ones as PDGF-Rβ kinase inhibitors

用比较分子场分析法(CoMFA)研究了一系列取代的吲哚-2-酮类化合物作为生长因子受体抑制剂对酪氨酸激酶PDGF-Rβ活性抑制作用的定量构效关系,建立了较好的预测模型,该模型非交叉验证的相关系数(R^2)为0.999,F值是1504.715,标准偏差(S)为0.042。根据该模型,设计并预测了数个新的化合物,表明该模型可定量地预测结构相近的类似物活性,为设计合成新的PDGF-Rβ酶抑制剂提供了理论依据。

Comparative molecular field analysis(CoMFA) was applied to performing a quantitative structureactivity relationship study on a set of substituted indol-2-ones as growth factor receptor inhibitors for PDGFRβ(platelet-derived growth factor receptor) tyrosine kinase inhibition, and a good predictive model was obtained. The relation coefficient (R^2) of non-cross validation for the model established by the study is 0.999, its F value is 1504.715 and the standard deviation(S) is 0.042. Several new compounds were designed andtheir activities predicted by the model. The result showed that the model can be used to quantitatively prognosticate the biological activity of analogues. Moreover, it provides a theoretical foundation for designing and synthesizing new PDGF-Rβ kinase inhibitors.