Synthesis and activity studies of analogues of the rat selective toxicant norbormide.
Norbormide [5-(alpha-hydroxy-alpha-2-pyridylbenzyl)-7-(alpha-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.
Rennison
David
D
Department of Chemistry, University of Auckland, 23 Symonds Street, Auckland, New Zealand. d.rennison@auckland.ac.nz
Bova
Sergio
S
Cavalli
Maurizio
M
Ricchelli
Fernanda
F
Zulian
Alessandra
A
Hopkins
Brian
B
Brimble
Margaret A
MA
D000818:Animals; D002855:Chromatography, Thin Layer; D003331:Coronary Vessels / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009636:Norbornanes / Q000138:chemical synthesis* / Q000633:toxicity*; D010539:Permeability / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012378:Rodenticides / Q000138:chemical synthesis*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000494:pharmacology
D007202:Indicators and Reagents; D009636:Norbornanes; D012378:Rodenticides; D014665:Vasodilator Agents; D011189:Potassium Chloride; C005321:norbormide