A QSAR study on a series of N-methyl pyrimidones acting as HIV integrase inhibitors

A quantitative structure-activity relationship (QSAR) study has been performed on integrase (IN) inhibition activity of a large series of N-methyl pyrimidones [Gardelli et al. (2007) J Med Chem 50, 4953-4975)] having varying heterocyclic ring substitution at 2-position of pyrimidone ring. The activity is found to be significantly correlated with surface tension and molar volume of the molecules. The whole series of compounds is divided into two subsets: a training set and a test set. A significant correlation is obtained for the training set, which is then used to predict the activity of compounds in the test set. The predicted activities of compounds in the test set are found to be very close to their observed activities. The predicting ability of the correlation obtained is judged by leave-one-out jackknife procedure. The correlation shows the effective role of the surface tension and molar volume of the molecules. From the correlation obtained, the integrase inhibition activities are predicted for some new prospective compounds.