Monoquatemary oximes

All four cholinesterase reactivator compounds are pralidoxlmes. The first two are monoquatemary oximes the last two are bisquatemary oximes. 

Another five monoquatemary oximes were prepared and tested in Croatia by Dr Kovarik s group (47) (Figure 66.40). All oximes inhibited human AChE reversibly. All prepared oximes reached reactivation of tabun-inhibited AChE within 24 h from 30 to 80% (Odzak et al., 2007). 

FIGURE 72.22 Structure of monoquatemary oximes from a study FIGURE 72.25 Monooxime-monocarbamoylbispyridinium xylene-... 

Monoquatemary pyridines with an oxime group in positions two (pralidoxime), three, and four (41) were prepared together with bisquatemary ones (42) connected via... 

Commonly used AChE reactivators have one (pralidox-ime) or two (HI-6) quaternary nitrogens in their molecules. According to our results, affinity of bisquatemary oximes towards intact and inhibited AChE is generally higher in comparison with monoquatemary ones (Kassa and Cabal, 1999 Kuca and Kassa, 2004). 

Odzak, R., Calic, M., Hrenar, T., Primozic, I., Kovarik, Z. (2007). Evaluation of monoquatemary pyridinium oximes potency to reactivate tabun-inhibited human acetylcholinesterase. Toxicology 233 85-96. 

Luo, C., Ashani. Y., and Doctor, B. P. (1998). Acceleration of oxime-induced reactivation of organophtrspliatc-inhibited fetal bovine serum acetylcholinc,sterase by monoquatemary and bisquatemary ligands. Mol. Pharmacol. 53,718-726. 

From a chemical point of view, standard AChE reactivators are monoquatemary or bisquatemary pyridinium salts bearing a functional oxime group in their molecules. The oxime is able to split the bond between the OP and enzyme. Consequently, free-functioning AChE is released. Unfortunately, none of the abovementioned AChE reactivators is effective against all known nerve agents and OP pesticides (Table 72.2 Kuca et al., 2007a). 

Monoquatemary pyridinium compounds with the oxime group in various positions (16 Figure 72.15) were prepared with bisquatemary ones (17 Figure 72.15) connected via a propane linker. Their reactivation ability was tested on tabun- and OP pesticide-inhibited cholinesterases. As predicted, trimedoxime reached the best activity compared with other oximes synthesized throughout the study (Musilek et al., 2006b,c). 

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