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目的建立CRTH2拮抗剂的3D-QSAR模型。方法采用比较力场分析(CoMFA)法和比较分子相似性指数分析(CoMSIA)法对103个炔基苯氧乙酸类CRTH2拮抗剂进行三维定量构效关系(3D-QSAR)研究,建立了具有良好预测能力的模型。结果 CoMFA法所建模型的交互验证系数q2为0.763,线性回归系数r2为0.931,最佳主成分数是6。CoMSIA法采用立体场、静电场、疏水场、氢键供体场所建模型性能最佳,其中q2和r2分别为0.644、0.904;最佳主成分数是6。结论 3D-QSAR模型及力场贡献值分析揭示了分子结构和结合常数间的关系,为今后的炔基苯氧乙酸类化合物的设计改造提供了更直接可行的线索。
Objective To establish a 3D-QSAR model of CRTH2 antagonist. Methods A three-dimensional quantitative structure-activity relationship (3D-QSAR) study of 103 alkynylphenoxyacetic acid CRTH2 antagonists was performed using comparative field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) Predictive ability of the model. Results The cross validation coefficient q2 of model established by CoMFA method was 0.763, the linear regression coefficient r2 was 0.931 and the best principal component was 6. CoMSIA method using the three-dimensional field, electrostatic field, hydrophobic field, hydrogen bond donor site modeling the best performance, of which q2 and r2 were 0.644,0.904; the best principal component is 6. Conclusion 3D-QSAR model and force field contribution analysis reveal the relationship between molecular structure and binding constants, and provide more direct and feasible clues for the design and modification of alkynylphenoxyacetic compounds in the future.