Discovery of novel benzo [b][1, 4] oxazin-3 (4H)-ones as poly (ADP-ribose) polymerase inhibitors

…, R Kamran, A Kiryanov, S O'Connell, E Taylor…

Index: Gangloff, Anthony R.; Brown, Jason; De Jong, Ron; Dougan, Douglas R.; Grimshaw, Charles E.; Hixon, Mark; Jennings, Andy; Kamran, Ruhi; Kiryanov, Andre; O'Connell, Shawn; Taylor, Ewan; Vu, Phong Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 16 p. 4501 - 4505

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Citation Number: 14

Abstract

Abstract Structure based drug design of a series of novel 1, 4-benzoxazin-3-one derived PARP-1 inhibitors are described. The synthesis, enzymatic & cellular activities and pharmacodynamic effects are described. Optimized analogs demonstrated inhibition of poly- ADP-ribosylation in SW620 tumor bearing nude mice through 24 h following a single dose.