Bulletin of the Korean Chemical Society, 32(5),1650-1656
Abstract
A series of potent tricyclic derivatives with a non-aromatic amide as potent PARP-1 inhibitors were successfully synthesized and their PARP-1 inhibitory activity was evaluated. Among the derivatives, 2-(1-propylpiperidin-4-yloxy)-7,8,9,10-tetrahydrophenanthridin-6(5H)-one 23c displayed potent activity in a PARP-1 enzymatic assay and cell-based assay (IC50 = 0.142 mu M, ED50 = 0.90 mu M) with good water solubility. Further, molecular modeling studies confirmed the obtained biological results.