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

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

  • Bioorg Med Chem Lett. 2013 Aug 15;23(16):4501-5. doi: 10.1016/j.bmcl.2013.06.055.
Anthony R Gangloff 1,  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

Affiliation

  • 1 Takeda California, 10410 Science Center Dr, San Diego, CA 92121, USA. anthony.gangloff@takeda.com
PMID: 23850199 DOI: 10.1016/j.bmcl.2013.06.055
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.

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