A 3-D QSAR study has been carried out on a new class of potent and selective human rhinovirus-14 (HRV-14) inhibitors. In particular, the CoMFA (comparative molecular field analysis) technique has been applied to develop a model able to explain and predict the anti-HRV-14 activity of a class of compounds 4 and potentially helpful to design new and more potent antirhinovirus agents. Docking experiments have also been performed with the aim of elucidating the possible binding mode of these inhibitors. These two approaches are combined to highlight a single, highly favoured mode of interaction of the compounds with the viral capsid proteins.