药物透过血脑屏障的3D-QSPR:H2受体拮抗剂的CoMFA和EVA分析

目的：药物透过血脑屏障是药代动力学的重要过程，H₂受体拮抗剂是作用于神经外周的抗溃疡药物,为避免该类药物透过血脑屏障损伤中枢神经，产生毒副作用，指导该类药物的设计与合成。方法和结果：选择了不依赖于实验参数的比较分子力场分析(CoMFA)方法和最近发展的本征值(EVA)方法，建立了有关的三维药代动力学性质(3D-QSPR)模型。CoMFA模型的统计参数为：交叉验证系数r²_cv=0.625，相关系数r2=0.893，F_3,17=47.270，标准偏差SE=0.254；EVA模型的统计参数为：交叉验证系数r²_cv=0.697，相关系数r²=0.922，F_3,17=67.766，标准偏差SE=0.203。结论：两种方法都能建立三维定量构效模型，EVA模型有更高的预测能力。

3D-QSPR OF BLOOD BRAIN BARRIER TRANSPORT FOR H2 RECEPTOR ANTAGONIST BY USING COMFA AND EVA METHOD

AIM: To built the model of blood brain barrier transport of 21 H2 receptor antagonists. METHODS AND RESULTS: The model was built by CoMFA (comparative molecular field analysis) and EVA (eigen values) method. Both CoMFA and EVA gave significant relationships with high crossvalidation correlation. The CoMFA model yielded a crossvalidation 0625 of r2cv, conventional r2 of 0893, F3,17=47270, and SE (Standard Error)=0254; the statistical parameters for the EVA model are 0697 of r2cv, conventional r2 of 0922, F3,17=67766, SE (Standard Error)=0203. CONCLUSION: The results showed that EVA model and CoMFA model have good predictive ability, but the EVA model showed higher predictive ability than the CoMFA model because it can exactly describe all properties of the molecule and is independent of the molecular alignment rule.