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. Epub 2013 Jun 24.

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.

MeSH terms

  • Animals
  • Benzoxazines / chemistry*
  • Benzoxazines / pharmacology*
  • Cell Line, Tumor
  • Drug Design*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Poly(ADP-ribose) Polymerase Inhibitors*

Substances

  • Benzoxazines
  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors