P450_(17α)抑制剂──17位取代甾体化合物的三维定量构效关系  

THREE DIMENSIONAL QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP OF P450_(17α) INHIBITORS OF 17-SUBSTITUTED STEROIDS

作　　者：苗及[1] 凌仰之[1] 朱娜[1] 雷小平[1] 

机构地区：[1]北京大学药学院药物化学系,北京100083

出　　处：《药学学报》2001年第7期507-510,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 (3 9670 85 5 )

摘　　要：目的　建立P45 0 1 7α的 17位取代甾体抑制剂的三维定量构效关系 ,为设计新的、更有效的抑制剂提供理论依据。方法和结果　利用比较分子力场方法 ,建立了P45 0 1 7α抑制剂的三维定量构效关系模型。交叉验证回归系数R2CV、非交叉验证回归系数R2 和标准偏差SEE分别为 0 5 38,0 799和 0 2 5 7。说明该系列化合物分子周围立体场和静电场的分布与生物活性间有良好的相关性。用该模型对本室合成的 3个化合物进行活性预测 ,结果与实测值相符。结论　所得模型支持了假设的抑制剂作用机理和作用模型。所得CoMFA模型有一定的预测能力 ,可用来指导设计新的P45 0 1AIM To develop a three dimensional quantitative structure activity relationship (3D QSAR) model and gain further insights into the requirements for potential P450 17α inhibitors. METHODS AND RESULTS A predictive 3D pharmacophore model was established based on comparative molecular field analysis (CoMFA). The correlation between the activities and structures was significant with cross validated value (R 2 cv ), non cross validated value (R 2) and standard error of estimate (SEE) of 0 538, 0 799 and 0 257, respectively. According to this model, the predicted inhibition activities of three compounds synthesized in our laboratory were compatible to actual activities. CONCLUSION This model would contribute to the understanding of the interaction between the inhibitors and P450 17α and rational design of novel lead molecules.

关 键 词：P45017α-抑制剂 比较分子场分析法 COMFA 三维定量构效关系 甾体化合物 

分 类 号：R977.3[医药卫生—药品] R914[医药卫生—药学]