Multivariate QSAR study of 4,5-dihydroxypyrimidine carboxamides as HIV-1 integrase inhibitors

A multivariate QSAR study of thirty-three 4,5-dihydroxypyrimidine carboxamides as HIV-1 integrase (HIV-1 IN) inhibitors was performed employing Ordered Predictors Selection (OPS) algorithm and PLS regression for variable selection and model construction, respectively. Four descriptors were chosen and a reasonable model (n = 30; R2 = 0.68; SEC = 0.57; PRESScal = 8.72; F(2,27) = 28.97; Q2LOO = 0.58; SEV = 0.62; PRESSval = 11.62; R2pred = 0.87; SEP = 0.29; AREpred = 4.37%; k = 0.99; k′ = 1.01; |r20 − r20′| = −0.18) was built with two latent variables (59.54% of the information). Leave-N-out (LNO) and Y-randomization methods confirmed the model robustness. The descriptors indicated that the HIV-1 IN inhibition depends on the electronic distribution of the investigated compounds. The interpretation of the model is related to the most accepted mechanism of action.

A multivariate quantitative structure–activity relationship (QSAR) study was developed for a series of 4,5-dihydroxypyrimidine carboxamides that present inhibition of strand transfer reaction catalyzed by HIV-1 integrase.Figure optionsDownload as PowerPoint slide