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

. 2013 Aug 15;23(16):4501-5.

doi: 10.1016/j.bmcl.2013.06.055. Epub 2013 Jun 24.

Jason Brown, Ron de Jong, Douglas R Dougan, Charles E Grimshaw, Mark Hixon, Andy Jennings, Ruhi Kamran, Andre Kiryanov, Shawn O'Connell, Ewan Taylor, Phong Vu

Affiliations

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

Anthony R Gangloff et al. Bioorg Med Chem Lett. 2013.

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 24h following a single dose.

Keywords: 1,4-Benzoxazin-3-one; Chemopotentiation; PARP-1; Poly(ADP-ribose)polymerase inhibitors; Structure-based drug design.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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