4616-24-4Relevant academic research and scientific papers
Stereoselective synthesis of the rat selective toxicant norbormide
Jay-Smith, Morgan,Murphy, Elaine C.,Shapiro, Lee,Eason, Charles T.,Brimble, Margaret A.,Rennison, David
, p. 5331 - 5342 (2016/08/04)
Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB, 1), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents/mammals. However, as an acute vasoactive, NRB has a rapid onset of action which makes it relatively unpalatable to rats, often leading to sub-lethal uptake/accompanying bait shyness. It is recognized that the pharmacological profile of NRB is highly sensitive to its stereoisomeric composition, yet no comprehensive endeavor has been made to impart any stereochemical control in its manufacture. The effect of temperature/concentration/reaction solvent/Lewis acid on the Diels–Alder synthesis of NRB is investigated. An attempted stereoselective synthesis of key NRB precursor 2-fulvenylmethanol 4 is also described. Palatability/efficacy data in rats is reported for novel NRB batches 1a–1e. Disappointingly, given the level of stereocontrol now available in the synthesis of NRB as a result of this research, no clear relationship between stereoisomeric composition and palatability was observed.
Synthesis and activity studies of analogues of the rat selective toxicant norbormide
Rennison, David,Bova, Sergio,Cavalli, Maurizio,Ricchelli, Fernanda,Zulian, Alessandra,Hopkins, Brian,Brimble, Margaret A.
, p. 2963 - 2974 (2008/02/01)
Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB, 1), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. A series of NRB-related analogues were prepared to investigate the structural features responsible for, and the in vitro biological markers indicative of, in vivo lethality of the parent molecule in rats. Their synthesis and biological evaluation (vasoconstriction, vasodilation, mitochondrial dysfunction, cardiotoxicity and lethality) is described.
