QSAR Studies of HEPT Derivatives as HIV-1 Reverse Transcriptase Inhibitors Using Physicochemical Parameters of Substituents
Yuan Zhou, Mei Ying Hu, Guizhao Liang, Yang Shan-bin, Zhiliang Li · Fain kemikaru · 2006
A novel substituent descriptor based on the physicochemical parameters about the electronic,hydrophobic and steric properties of substituents is used to describe the chemical structures of 6-(phenylthio) thymine HEPT analogues.The variables are reduced using stepwise multiple regression(SMR) method for the training set,and the statistical results indicate that squares of the correlation coefficients in the multiple linear regression and cross validation using leave one out(LOO) are 0.904 and 0.848 7,respectively.To validate the predictive capability of resulting models,external validation are performed with R~2_(ext) and Q~2_(ext) values of 0.928 9 and 0.929 4,respectively.The models obtained shows that the X substituents in 5-position of the thymine ring have more activity on HIV-1 reverse transcriptase than that of the 6phenylthio groups,and the weak electronic and hydrophobic effects of the X substituents in 5-position can enhance the anti-viral activity.