Synthesis of isoquinolinone-based tricycles as novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors

Bioorg Med Chem Lett. 2014 Jun 15;24(12):2669-73. doi: 10.1016/j.bmcl.2014.04.061. Epub 2014 Apr 24.

Abstract

The isoquinolinone-based tricyclic compounds were designed and synthesized. Preliminary biological study of these compounds provided potent compounds 17a, 33b, 33c, 33d, and 33g with low nanomolar IC50s against PARP-1 enzyme.

Keywords: Antitumor; Isoquinolinone-based tricycles; PARP-1 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Isoquinolines / chemistry*
  • Isoquinolines / pharmacology*
  • Molecular Structure
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Poly(ADP-ribose) Polymerases / chemistry

Substances

  • Enzyme Inhibitors
  • Isoquinolines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases