2,4-二芳基-1,3-二硫戊环化合物的定量构效关系研究

QSAR Study on 2,4-Diaryl-1,3-Dithiolane Thiourea and Isothiourea Compounds

目的 为进一步设计和研究 2 ,4-二芳基 - 1,3 -二硫戊环类化合物提供可参考依据。方法 对合成的 68个 2 ,4-二芳基 - 1,3 -二硫戊环化合物以 POL YGEN软件中的 CHARMm程序对其活性化合物的结构进行计算机分子模拟。根据所得化合物的能量最低构象 ,计算了其 VDW体积、偶极矩、总键能、总键角能、总非正则能以及硫原子电荷等值 ,将其结果作为结构参数分别与这些化合物的 i NOS抑制活性进行相关分析。结果 以逐步回归法建立了相关性方程 :- log IC50 =2 .2 847+ 0 .10 5 2 X3+ 0 .0 5 89X6 - 0 .0 0 44 X1 8( n=16,R=0 .919466,S=0 .7112 2 5 ,F=2 1.8760 5 )。结论 二硫戊环类化合物的 i NOS抑制活性与分子总键角能、分子总范德华能呈正相关 ,与二硫戊环 2位芳基相连

AIM To offer reference for further research of 2, 4-diaryl-1, 3-dithiolane compounds. METHODS Structures of 2, 4-diaryl-1, 3-dithiolane compounds were mimicked by computer-aided molecular modeling. The POLYGEN software and the method of clique coordinate transformation were involved in these modeling processes. RESULTS 20 parameters were calculated by MM 2 and CNDO/2 methods. Significant correlation equation between the calculated structural parameters and iNOS inhibitory activity of the compounds was established by stepwise regression analysis:-logIC 50=2.2847+0.1052 X 3+0.0589X 6-0.0044X 18 (n=16,R=0.919466,S=0.711225,F=21.87605 ). CONCLUSION The QSAR equations showed that the iNOS inhibitory activity of these compounds increased with the increase of angle energy of molecular and Lennard-Jones energy of molecular while decreased with the increase of N 2 atom charge.