Synthesis of substituted 5[H]phenanthridin-6-ones as potent poly(ADP-ribose)polymerase-1 (PARP1) inhibitors

Bioorg Med Chem Lett. 2001 Jul 9;11(13):1687-90. doi: 10.1016/s0960-894x(01)00281-5.


1-, 2-, 3-, 4-, 8-, or 10-Substituted 5(H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared, some showed not only low IC(50) values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5(H)phenanthridin-6-one ring.

MeSH terms

  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Phenanthridines / chemical synthesis*
  • Phenanthridines / chemistry
  • Phenanthridines / pharmacology*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Structure-Activity Relationship


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