Identification and SAR of novel pyrrolo[1,2-a]pyrazin-1(2H)-one derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1).

By Pescatore, Giovanna; Branca, Danila; Fiore, Fabrizio; Kinzel, Olaf; Bufi, Laura Llauger; Muraglia, Ester; Orvieto, Federica; Rowley, Michael; Toniatti, Carlo; Torrisi, Caterina; et al
From Bioorganic & Medicinal Chemistry Letters (2010), 20(3), 1094-1099. Language: English, Database: CAPLUS, DOI:10.1016/j.bmcl.2009.12.026

The discovery of a novel series of pyrrolo[1,2-a]pyrazin-1(2H)-one PARP inhibitors is described. Optimization led to compds. that display excellent PARP-1 enzyme potency and inhibit the proliferation of BRCA deficient cells in the low double-digit nanomolar range showing excellent selectivity over BRCA proficient cancer cells.