Design of new imidazole derivatives with anti-HCMV activity: QSAR modeling, synthesis and biological testing

The problem of designing new antiviral drugs against Human Cytomegalovirus (HCMV) was addressed using the Online Chemical Modeling Environment (OCHEM). Data on compound antiviral activity to human organisms were collected from the literature and uploaded in the OCHEM database. The predictive ability of the regression models was tested through cross-validation, giving coefficient of determination q² = 0.71-0.76. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with reasonable accuracy within the applicability domain (q² = 0.70-0.74). The models were applied to screen a virtual chemical library of imidazole derivatives, which was designed to have antiviral activity. The six most promising compounds were identified, synthesized and their antiviral activities against HCMV were evaluated in vitro. However, only two of them showed some activity against the HCMV AD169 strain.