关键词: 环尿素类化合物, N,N-二甲基-2-溴苯乙胺类衍生物, 取代基物化参数, 定量构效关系

Abstract: A novel substituent descriptor based on the 17 different physicochemical parameters about the electronic, hydrophobic and steric properties of substituents is used to describe the chemical structures of 22 cyclic ureas and 22 N,N-dimethyl-2-bromo(substituted phenyl) ethylamine derivatives, respectively. The variables are reduced using stepwise multiple regression (SMR) method for the training set, and the statistical results indicate that the correlation coefficient square for the two series of compounds in the multiple linear regression and cross validation using leave one out (LOO) is 0.853, 0.960, 0.723 and 0.901, respectively. To validate the predictive power of resulting models, external validation are performed for two testing sets with Qext2 values of 0.7617 and 0.7653, respectively. The models obtained also shows that the anti-HIV activity of cyclic ureas is blocked by steric hindrance of ortho and para substituents and hydrophobicity of meta and para substituents, the biological activity of N,N-dimethyl-2-bromo (substituted phenyl) ethylamine derivatives may be improved by introducing the steric substituents and electronic supplying para substituents into phenyl ring.

Key words: Cyclic ureas, N,N-dimethyl-2-bromo(substituted phenyl) ethylamine derivatives, Physicochemical parameters of substituent, Quantitative structure activity relationship (QSAR)