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

作　　者：孙运佳[1] 吉海东[1] 毛卫娟[1] 刘嘉洲 韩正政 冯长君[1] 

机构地区：[1]徐州工程学院化学化工学院,江苏徐州221111

出　　处：《化学研究与应用》2015年第4期483-488,共6页Chemical Research and Application

基　　金：国家自然科学基金项目(21075138)资助;环境模拟与污染控制国家重点联合实验室开放基金项目(13K02ESPCT)资助;徐州市科技局基金项目(XM13B111)资助

摘　　要：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.

关 键 词：嘧啶吗啉苯甲酰胺衍生物 HEDGEHOG信号通路 抑制活性 电性距离矢量 构效关系 

分 类 号：R730.231.1[医药卫生—肿瘤] O6-051[医药卫生—临床医学]