含双叔丁基苯基杂环化合物的三维定量构效关系研究  

THREE DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF HETEROCYCLIC-COMPOUNDS WITH DI-TERT-BULTYLPHENYL INHIBITORS

作　　者：柏爱萍[1] 郭宗儒[1] 褚凤鸣[1] 

机构地区：[1]中国医学科学院,中国协和医科大学药物研究所,北京100050

出　　处：《药学学报》2001年第5期347-350,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目!(39770 877)

摘　　要：目的　建立两环系环氧合酶 2抑制剂的三维定量构效关系 ,设计新型环氧合酶 2抑制剂。方法和结果通过与选定的模板 (III 1)进行叠合 ,利用比较分子力场分析方法建立 2 0个选择性环氧合酶 2抑制剂的三维定量构效关系。该模型的交叉验证系数RCV2 =0 718;传统相关系数R2 =0 992 ,F =2 6 0 6 2 4,标准偏差S =0 0 72。结论所得的模型解释了已有的构效关系 ,并对同类化合物的预测能力较好 。AIM To quatitatively disclose the relationship between activity and structure of a new class of COX II inhibitors containing dialkylphenyl linked heterocyclic moieties. METHODS AND RESULTS Seventeen COX II inhibitors from literature as a training set were investigated with the aim of developing a 3D QSAR model using comparative molecular field analysis (CoMFA). To reveal the pharmacophoric pattern, several modes of superimposition were explored. The significant model shows a higher ability to explain and predict the activity of COX II inhibitors, with the cross validation R CV 2=0 718, non cross validation R 2=0 992, F=260 624, and SEE (standard error of estimate)=0 072. Three compounds were selected as a predicting set, the low deviations of calculated values from the measured ones suggesting a powerful predictive ability of the model. CONCLUSION The 3D QSAR explains the dependence of COX 2 inhibition upon the structures of the compounds. Some structure information for design of new COX II inhibitors with higher activity has been given.

关 键 词：环氧合酶-2 比较分子力场 双叔丁基苯基杂环化合物 抑制剂 抗炎药 

分 类 号：R971.1[医药卫生—药品] R917[医药卫生—药学]