Scaffold‐Hopping Cascade Yields Potent Inhibitors of 5‐Lipoxygenase

A two-step iterative approach to virtual screening can identify potent lead scaffolds as demonstrated for 5-lipoxygenase inhibition, a validated target for the treatment of inflammation and allergic reactions. Four cycles of virtual screening using both 3D- and 2D-based methods, and substructure searching were performed, and cell-based assays were used to further refine the lead selection at each stage of the process.