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用量子化学密度泛函、分子力学及统计方法,对二烷氧基喹唑啉衍生物进行定量构效关系(QSAR)研究。由计算所得的化合物分子的几何结构、电子结构参数和分子性质为广义描述符(变量),通过逐步回归分析,筛选出主要因素,建立QSAR方程。结果表明化合物的偶极距(μ),A环C_1和C_3原子的净电荷(Q_(C1)和Q_(C3))以及取代基R_7的立体参数(MR_7)是影响化合物抑制活性的主要因素。方程的拟合相关系数(r~2)和交叉验证系数(q~2)分别为0.874和0.8093,表明方程具有良好的预测能力,可用于预测未知化合物的活性。基于此QSAR方程,设计了4个具有较高抑制活性的新的化合物并有待实验的验证。
Quantitative structure-activity relationship (QSAR) studies of dialkoxyquinazoline derivatives were carried out using quantum chemical density functional theory, molecular mechanics and statistical methods. The geometrical structure, electronic structure parameters and molecular properties of the calculated compounds are generalized descriptors (variables). Through stepwise regression analysis, the main factors are screened and the QSAR equation is established. The results showed that the dipole moment (μ), the net charge (Q_ (C1) and Q_ (C3)) and the stereo parameter (R_7) of substituents C_1 and C_3 of A ring were the main factors affecting the inhibitory activity of the compounds. The fitting correlation coefficient (r ~ 2) and cross validation coefficient (q ~ 2) of the equation are 0.874 and 0.8093, respectively, indicating that the equation has good predictive ability and can be used to predict the activity of unknown compounds. Based on this QSAR equation, four new compounds with higher inhibitory activity were designed and validated experimentally.