芳构酶抑制剂7α-取代雄甾二酮三维定量构效关系的研究

Three demensional quantitativestructure-activity relationships of 7α-substitutedandrostenedione as aromatase inhibitors

目的建立 7α 取代雄甾二酮芳构酶抑制剂的三维定量构效模型 ,为设计高效芳构酶抑制提供理论依据。方法利用比较分子力场分析方法 ,建立了 3 0个 7α 取代雄甾二酮芳构酶抑制剂的三维定量构效模型。结果该模型的交叉验证相关系数R2cv=0 72 1,非交叉验证相关系数R2 =0 994,标准偏差SE =0 0 62 ,F =170 787。用此模型预测了 4个芳构酶抑制剂的活性 ,结果与实验值相符。结论该模型有较高的预测能力 。

Aim To build a three dimensional structure activity relationship model and gain further insights into the requirements for potential steroid aromatase inhibitors.Method A 3D QSAR model of thirty aromatase inhibitors was established by the comparative molecular field analysis (CoMFA) method.The result of cross validated R 2 cv =0 721,non cross validated R 2=0 994, SE (standard error)=0 062,and F =170 787.The activities of the four aromatase inhibitors were predicted by this mode and the results were compatible to actual values.Result and Conclusion The model possesses a high predictability and offers an approach to design the new aromatase inhibitors.