Identification of phosphodiesterase-1 and 5 dual inhibitors by a ligand-based virtual screening optimized for lead evolution

We identified new lead candidates which showed potent dual inhibition against phosphodiesterase-1 and 5 by a ligand-based virtual screening optimized for lead evolution. This virtual screening method, consisting of classification and regression tree analysis using 168 2-center pharmacophore descriptors and 12 macroscopic descriptors, demonstrated a high predictive ability for bioactivity of new chemical compounds. The obtained lead candidates were structurally diverse, although only the structure–activity relationship data of hydroxamic acid derivatives were used to configure the prediction model for the virtual screening.