A QSAR study on a series of thiourea derivatives acting as anti-hepatitis C virus agents.

ABSTRACT

A quantitative structure-activity relationship (QSAR) study was performed on a large series of thiourea derivatives reported by Kang et al. [Bioorg Med Chem Lett (2009), 19, 1950-55 & 6063-68], acting as anti-hepatitis C virus (anti-HCV) agents. The activity of the compounds was found to be significantly correlated with their hydrophobic property and three indicator variables I1, I2 and I3, the first two specifying a negative effect of an alkyl and an aromatic group, respectively on their R-moiety and the third one specifying a negative effect of their Ar-moiety having a nitrogen-containing heterocyclic ring. The whole set containing 85 compounds was divided into two subsets the training set and the test set containing 61 and 24 compounds, respectively. For the training set, the correlation coefficient (r) and the square of cross-validated correlation coefficient (r2cv) were found to be 0.926 and 0.83, respectively. The correlation obtained suggested that anti-HCV activity of the compounds would depend on their hydrophobic property, conformational flexibility and the steric effects of an alkyl or an aromatic group on the R-moiety. This suggested that the molecules might have significant hydrophobic interactions with the receptor which might be aided by their conformational flexibility, but hindered sterically by an alkyl or an aromatic group on their R-moiety. Using the correlation obtained, some new compounds having activity higher (>8.0) than the most active compound in the existing series were predicted.