三唑硫醚类药物与抑制大鼠反应性关节炎活性的构效关系研究

Study on QSAR between 1,5-diphenyl-1,2,4-triazoles and its anti-adjuvant arthritis in rats

目的建立1,5-二苯基-1,2,4-三唑硫醚类化合物的分子结构与抑制大鼠反应性关节炎活性的定量构效关系(QSAR)模型。方法采用Gaussian03程序中的HF/6-31G法计算15种三唑硫醚化合物的结构参数,结合其对大鼠反应性关节炎抑制活性的实验值,进行多元线性回归。结果建立了具有良好稳定的QSAR模型:-lgIC=26.483+0.033CV+12.187QC4-H+1.055QC10+28.718QN1。结论 1,5-二苯基-1,2,4-三唑硫醚化合物抑制大鼠反应性关节炎的活性随CV、QC4-H、QC10和QN1的增大而增强。

Objective To establish quantitative structure-activity relationship（QSAR） between quantum chemical parameters of 3-（alkyllthio）-1,5-diphenyl-1,2,4-triazoles and anti-adjuvant arthritis in rats.Methods Structural and thermodynamic parameters of a series of 1,5-diphenyl-1,2,4-triazole derivatives were computed at the HF/ 6-31G level in Gaussian03 program.The correlation between anti-adjuvant arthritis of these compounds and the obtained structural and thermodynamic parameters was analyzed by multiple linear regression techniques.Results The QSAR model was established as follows：-lgIC=26.483＋0.033CV＋12.187QC4-H＋1.055QC10＋28.718QN1.Conclusion Anti-adjuvant arthritis of 3-（alkyllthio）-1,5-diphenyl-1H-1,2,4-triazoles to rats was increasing with the increase of molar constant-volume heat capacity（CV）,the charge of hydrogen atom combined with NO.4 carbon（QC4-H）,the charge of NO.10 carbon（QC10） and the charge of N1 nitrogen atoms（QN1）.