Exploring Simple Drug Scaffolds from the Generated Database Chemical Space Reveals a Chiral Bicyclic Azepane with Potent Neuropharmacology

To assess how much structural diversity remains unexploited in simple drug scaffolds, we investigated ring systems functionalized with amine handles. Starting from the ring systems database GDB-4c, we enumerated 1139 possible amines and diamines with up to two five-, six-, or seven-membered rings. From the 680 cases not listed in PubChem, we synthesized several unprecedented cis- and trans-fused azepanes and tested possible targets predicted using the polypharmacology browser PPB2. From this...