3D-QSAR of 2,5-disubstituted-1,3,4-thiadiazole derivatives as diuretic agents: A comparative molecular field analysis study

A three-dimensional quantitative structure activity relationship (3D-QSAR) study using comparative molecular field analysis (CoMFA) method was performed on 2,5-disubstituted1,3,4-thiadiazole derivatives as diuretic agents. This study was performed using 40 compounds, in which the CoMFA model was developed using a training set of 30 compounds. Ten compounds (selected at randomly served as a test set), which were not used in model generation, were used to validate the CoMFA model. CoMFA derived QSAR model shows a good conventional squared correlation coefficient r and cross validated correlation coefficient rcv 0.976 and 0.579 respectively. In this analysis steric and electrostatic field contribute to the QSAR equation by 73.8% and 26.2% respectively, suggesting that variation in biological activity of the compounds is dominated by differences in steric (van der Waals) interactions. To visualize the CoMFA steric and electrostatic field from PLS analysis, contour maps are plotted as percentage contribution to the QSAR equation and are associated with the differences in biological activity.