Comparative molecular field analysis of HIV-1 reverse transcriptase inhibitors in the class of 1[(2-hydroxyethoxy)-methyl]-6(phenylthio)thymine

A Comparative Molecular Field Analysis of 40 HEPT (1-[(2-Hydroxyethoxy)-methyl]-6-(phenylthio)thymine) analogues was performed. The 3D-QSAR study correlates steric and electrostatic fields of the compounds with HIV-1 RT inhibition, resulting in a model which has a high predictive ability. CoMFA results revealed that steric interaction explains a majority (70%) of the variance in the data. Using only steric interaction energy in the analyses provided a better predictive model. Inclusion of electrostatic descriptors in terms of coulomb interaction energies deteriorates the results. However, it was found in this study that variation of sp(3) O charges had some influence on r(cv)(2) and that the interaction energies using sp(3) O probe with a charge of -0.3 led to the best predictive model.