Highly potent poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors, including 9-hydroxy-1, 2- dihydro-4H-thiopyrano [3, 4-c] quinolin-5 (6H)-one derivatives with a non-aromatic A-ring, were synthesized. Among the derivatives, 12a showed low nanomolar enzyme and cellular activity (IC50= 42nM, ED50= 220nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo.
