The design, synthesis, and biological evaluation of a series of new aromatase (AR, CYP19) inhibitors bearing an imidazole ring linked to a 7-substituted coumarin scaffold at position 4 (or 3) are reported. Many compounds exhibited an aromatase inhibitory potency in the nanomolar range along with a high selectivity over 17-α-hydroxylase/C17-20 lyase (CYP17). The most potent AR inhibitor was the 7-(3,4-difluorophenoxy)-4-imidazolylmethyl coumarin 24 endowed with an IC(50) = 47 nM. Docking simulations on a selected number of coumarin derivatives allowed the identification of the most important interactions driving the binding and clearly indicated the allowed and disallowed regions for appropriate structural modifications of coumarins and closely related heterocyclic molecular scaffolds.