Discovery and SAR of novel, potent and selective hexahydrobenzonaphthyridinone inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1).

By Torrisi, Caterina; Bisbocci, Monica; Ingenito, Raffaele; Ontoria, Jesus M.; Rowley, Michael; Schultz-Fademrecht, Carsten; Toniatti, Carlo; Jones, Philip
From Bioorganic & Medicinal Chemistry Letters (2010), 20(2), 448-452. Language: English, Database: CAPLUS, DOI:10.1016/j.bmcl.2009.12.002

A novel hexahydrobenzonaphthyridinone PARP-1 pharmacophore is reported. Subsequent SAR exploration around this scaffold led to selective PARP-1 inhibitors with low nanomolar enzyme potency, displaying good cellular activity and promising rat PK properties.