A series of C-5 modified 3-iodo-4-aryloxypyridinones (IOPYs) and 3-iodo-4-arylthio- pyridinones (ISPYs) serves as a potential class of HIV-1 non-nucleoside reverse transcriptase inhibitors. These two pyridinone analogues are attracting more attentions mainly due to their potential abilities to simultaneously inhibit wild type and mutant HIV-1 strains. In this study, two sets of traditional two-dimensional descriptors were applied respectively to create linear and binary QSAR models for these compounds. Our results indicated the well prediction ability of the obtained models. It is also indicated that binary model achieved a better prediction results than the linear one. Furthermore, in order to obtain a better description of the structure characteristics of the HIV-1 reverse transcriptase inhibitors, 3D-QSAR models and SAReport analysis were used to explore the compound features which contribute to the inhibition of wild type as well as mutant HIV-1 strains. Our analysis reveals that there may existed three principles to follow when the compounds are modified: (i) the electrostatic potentials distribution of R-groups plays a key role in determining the biological activities of the compounds|(ii) an aromatic ring or aromatic heterocycle for R-groups is favorable to enhance the biological activity|and finally (iii) the number of substituents attached to the ring of R-groups should be appropriate.

Key words: QSAR, non-nucleoside reverse transcriptase inhibitors, HIV-1, pyridinone derivatives