2-nitroimidazol-5-ylmethyl as a potential bioreductively activated prodrug system: reductively triggered release of the PARP inhibitor 5-bromoisoquinolinone

Bioorg Med Chem Lett. 1999 Jul 19;9(14):2031-6. doi: 10.1016/s0960-894x(99)00306-6.

Abstract

5-Chloromethyl-1-methyl-2-nitroimidazole reacted efficiently with the anion derived from 5-bromoisoquinolin-1-one to give 5-bromo-2-((1-methyl-2-nitroimidazol-5-yl)methyl)isoquinolin -1-one. Biomimetic reduction effected release of the 5-bromoisoquinolin-1-one. The 2-nitroimidazol-5-ylmethyl unit thus has potential for development as a general prodrug system for selective drug delivery to hypoxic tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonium Chloride / chemistry
  • Chromatography, High Pressure Liquid
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism*
  • Hypoxia
  • Imidazoles / chemistry*
  • Imidazoles / metabolism*
  • Isoquinolines / chemistry
  • Isoquinolines / metabolism*
  • Oxidation-Reduction
  • Palladium / chemistry
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Prodrugs / chemistry*
  • Prodrugs / metabolism*
  • Quinolones / chemistry*
  • Quinolones / metabolism*
  • Zinc / chemistry

Substances

  • 5-bromo-2-((1-methyl-2-nitroimidazol-5-yl)methyl)isoquinolin-1-one
  • 5-bromoisoquinolin-1-one
  • Enzyme Inhibitors
  • Imidazoles
  • Isoquinolines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Prodrugs
  • Quinolones
  • Ammonium Chloride
  • Palladium
  • Zinc