Design and synthesis of prodrugs of the rat selective toxicant norbormide

Bioorg Med Chem. 2012 Jul 1;20(13):3997-4011. doi: 10.1016/j.bmc.2012.05.014. Epub 2012 May 15.


Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, one major drawback of NRB as a viable rodenticide relates to an evolutionary aversion developed by the rat leading to sub-lethal dosing due to either its unpleasant 'taste' or rapid onset of effects. A series of NRB prodrugs were prepared in an effort to 'mask' this acute response. Their synthesis and biological evaluation (in vitro vasoconstrictory activity, in vitro hydrolytic and enzymatic stability and lethality/palatability in vivo) is described. Compound 19 displayed the most promising profile with respect to a delay in the onset of symptoms and was subsequently demonstrated to be significantly more palatable to rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Design*
  • Enzymes / metabolism
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Imides / chemical synthesis*
  • Imides / metabolism
  • Imides / toxicity
  • Liver / enzymology
  • Liver / metabolism
  • Norbornanes / chemical synthesis*
  • Norbornanes / metabolism
  • Norbornanes / toxicity
  • Prodrugs / chemical synthesis*
  • Prodrugs / metabolism
  • Prodrugs / toxicity
  • Rats
  • Rodenticides / chemical synthesis*
  • Rodenticides / metabolism
  • Rodenticides / toxicity
  • Vasoconstriction / drug effects


  • Enzymes
  • Imides
  • N-cinnamoyloxymethyl-5-(alpha-hydroxy-alpha-2-pyridylbenzyl)-7-(alpha-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide
  • Norbornanes
  • Prodrugs
  • Rodenticides
  • norbormide