三嗪噁二唑基吡唑衍生物抑酶活性的QSAR模型

QSAR Models for the Inhibitory Enzyme Activities of Triazinyl-Oxadiazolyl-Pyrazole Derivatives

基于拓扑化学理论,原子类型电拓扑态指数(Mk)被用于表征18种三嗪噁二唑基吡唑衍生物的化学微环境。采用最佳变量子集回归方法,分别建立上述化合物对蛋白酪氨酸磷酸酯酶1B(PTP1B)、细胞分裂周期25磷酸酯酶B(Cdc25B)的抑酶活性(P_t、C_d)与Mk的定量构效关系(QSAR)模型。它们的最佳三元QSAR模型的判定系数(R^2)依次为0.896、0.828,逐一剔除法交叉验证相关系数(R_(cv)~2)依次为0.830、0.688。经R_(cv)~2、VIF、FT、AC等检验,该模型具有良好的稳健性及预测能力。经训练集验证,上述模型均具有良好的外部预测能力。模型显示,影响Pt、Cd的因素既有不同的结构基团(-CH_3、-O-、-NH_2和芳环中-N=),也有相同的因素(芳环中-C=)。

Based on topological chemical theory,electrotopological state indice（ Mk） of atom type were used to describe the chemical microenvionment of 18 triazinyl-oxadiazolyl-pyrazole derivatives. The Quantitative StructureActivity Relationship（ QSAR） models for the inhibitory enzyme activities（ Pt,Cd） of above compounds to protein tyrosine phosphatase 1 B（ PTP1 B） and cell division cycle 25 phosphatase B（ Cdc25 B） was developed based on the Mk and leaps-and-bounds regression,respectively. The coefficient of multiple determination（ R^2） and cross-validated coefficient of multiple determination（ Rcv2） of leave-one-out（ LOO） of the optimal three variable QSAR model for Pt were 0. 896,0. 830,respectively. R2 and Rcv2 of the optimal three variable QSAR model for Cdwere 0. 828,0. 688,respectively. The QSAR model has both favorable estimation stability and good prediction capability by Rcv2,VIF,FT,ACtests. Verified by the training set,the models have good external prediction ability. The models showed that dominant influence factors of Pt,Cdare different structural groups（-CH3,-O-,-NH2 and-N = in aromatic rings） as well as the same factors（-C = in aromatic rings）.