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ID: ALA1153757

Journal: Eur J Med Chem

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

Authors: de Melo EB, Ferreira MM.

Abstract: 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; R(2)=0.68; SEC=0.57; PRESS(cal)=8.72; F((2,27))=28.97; Q(2)(LOO)=0.58; SEV=0.62; PRESS(val)=11.62; R(2)(pred)=0.87; SEP=0.29; ARE(pred)=4.37%; k=0.99; k'=1.01; |r(2)(0)-r(2)(0)'|=-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.

CiteXplore: 19327872

DOI: 10.1016/j.ejmech.2009.03.001