选择性环氧合酶-2抑制剂的三维定量构效研究

THREE DIMENSIONAL QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP OF SELECTIVE CYCLOOXYGENASE 2 INHIBITORS

目的：建立环氧合酶２选择性抑制剂的三维构效关系，设计新型的环氧合酶２抑制剂。方法和结果：通过４４个抑制剂与环氧合酶２的对接确定分子的叠合模式，利用比较分子力场分析方法建立了４４个选择性环氧合酶２抑制剂的三维定量构效模型。模型的交叉验证系数ＲＣＶ２＝０７０９，传统相关系数ＲＣＶ２＝０９１１，Ｆ５，３８＝７５６６，标准偏差ＳＥ＝０２４２。结论：利用ＤＯＣＫ和ＣｏＭＦＡ相结合的方法提供了分子设计的新途径。

AIM: The discovery of cyclooxygenase 2(COX 2) provides a new target for designing nonsteroidal anti inflammatory drugs(NSAIDs) with less side effects. A series of inhibitors were analyzed in order to disclose the relationship between activity and structure. METHODS AND RESULTS: Forty four selective COX 2 inhibitors were investigated by means of dock and comparative molecular field analysis(CoMFA). Based upon the active conformation extracted from the SC 558/COX 2 complex all inhibitors were docked into receptor and aligned. The model from dock CoMFA showed higher ability to explain and predict the activity of selective COX 2 inhibitors, cross validated R cv 2=0 709, non cross validated r 2=0 911, F 5,38 =75 606, SE=0 242. CONCLUSION: The combination of dock CoMFA offers an approach to design new molecule.