engleski

Synthesis of Iimidazolio-Quinuclidinium Oximes: Potential Antidotes against Organophosphorus Poisoning

It is known that antidotal properties of 3- hydroxyquinuclidinium derivatives are the consequence of their interaction with acetycholinesterase (AChE) and/or other receptors in the cholinergic system (1). On the other hand, the primary antidotal effect of imidazolium oximes is reactivation of phosphorylated AChE. Several imidazolio-quinuclidinium oximes have been synthesized in order to investigate the properties of compounds containing both moieties in the same molecule. We describe the synthesis of N-(3-(2- hydroxyiminomethyl-3-methyl-1-imidazolio)propyl-3- oxoquinuclidinium diiodide (I) and N-(3-(2- hydroxyiminomethyl-3-methyl-1-imidazolio)-2- oxapropyl derivatives of 3-oxo (II), 3-hydroxy (III), 3-dimethylcarbamoyloxy (IV) and 3-acetyloxy (V) quinuclidines. Different substituents have been introduced in the 3-position of the quinuclidinium moiety in attempt to increase biological activity of new compounds. Furthermore, compound I was synthesized to evaluate the possible importance of oxygen instead of carbon in the chain connecting quinuclidinium and imidazolium parts. Synthesized compounds were studied for their mode of binding to AChE, their effect upon phosphorylation of AChE by Soman and VX and their effect upon Soman intoxicated mice (2).

imidazolio-quinuclidinium oximes

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