苯甲酰胺衍生物对Hh信号通路抑制的理论研究

Theoretical study on the inhibition activity of 4-( Pyrimidin-2-ylamino) benzamide derivatives to hedgehog signaling pathway

基于拓扑方法计算了16种嘧啶吗啉苯甲酰胺衍生物的电性距离矢量(Mt)。通过最佳变量子集回归建立其对Hedgehog信号通路抑制活性(IC50)与Mt的最佳三元数学模型(QSAR),其判定系数(R2)及逐一剔除法的交叉验证相关系数(Rcv2)分别为0.832、0.600。经Rcv2、VIF、FIT、AIC等检验,该模型具有良好的稳健性及预测能力。根据进入此模型的M66,M18,M2可知,影响嘧啶吗啉苯甲酰胺衍生物对Hedgehog信号通路抑制活性的主要因素是分子的二维结构特征CH3-、-CHf-、-NHg-、>N-和HO-等结构碎片。

The electronegativity distance vector（ Mt） of 16 pyrimidin-morpholine benzamide derivatives were calculated by topological method. The quantitative structure-activity relationships（ QSAR） was established by using leaps-and-bounds regression analysis for the inhibition activity（ IC50） of above compounds to hedgehog signaling pathway along with the Mt. The traditional correlation coefficient（ R2） and the cross-validation correlation coefficient（ Rcv2） of leave-one-out（ LOO） are 0. 832 and 0. 600,respectively. The QSAR models have both favorable estimation stability and good prediction capability by Rcv2,VIF,FIT,AICtests. M66,M18,M2 in the model shows that the main factor to affect the inhibition activity of pyrimidin-morpholine benzamide derivatives is a two-dimensional structural characteristics of the molecular CH3-,- CHf-,- NHg-, N- and HO- structure fragments.