Synthesis and Research of Reactivation of Phosphorylated Cholinesterase by Quaternary Pyridinium-Aldoxime Salts

Ludmila Bobkova
Affiliation: 
State Institution “Institute of Pharmacology and Toxicology of National Academy of Sciences of Ukraine”, 14, Eugene Potie str., 03680 Kyiv, Ukraine; ift-bobkova@rambler.ru
DOI: 
https://doi.org/10.23939/chcht09.03.281
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Abstract: 
The interaction of pyridine-4(-3,-2)aldoxime has been studied whit 3-bromo-N,N,N-trialkyl-2-oxo(-hydroxyimino)-1-propanaminium bromide. The structure of all synthesized compounds was determined by elemental analysis as well as by physical and chemical methods. All synthesized compounds were tested for reactivation of phosphorylated acetylcholinesterase. Using fragments of the molecules (an oxime group, 3-bromo-N,N,N-trimethyl(or triethyl)ammonium [(or N-methyl-morpholinium)-2-oxo(or 2-hydroxyimino)]propan bromides), a new series of pyridinium-aldoxime salt (cholinesterase reactivator) was obtained.
References: 

[1] Mars T.: Pharmacol. Ther., 1993, 58, 51.
https://doi.org/10.1016/0163-7258(93)90066-M

[2] Bajar J.: Adv. Clin. Chem., 2004, 38, 151.
https://doi.org/10.1016/S0065-2423(04)38006-6

[3] Buriak V., Zopia B. et al.: Nats. Nauk.-Techn. Conf., Ukraine, Lviv 2008, 191.

[4] Musilek K., Kuca K., Jun D. et al.: Curr. Org., 2007, 11, 229.
https://doi.org/10.2174/138527207779316417

[5] Kuca K., Bielavsky J., Cabal J. et al.: Tetrahedron Lett., 2003,44, 3123.
https://doi.org/10.1016/S0040-4039(03)00538-0

[6] Musilek K., Jun D., Cabal J. et al.: J. Med. Chem., 2007, 50, 5514.
https://doi.org/10.1021/jm070653r

[7] Cabell L.: Pat. US 2009/0281144 A1, Publ. Nov. 12, 2009.

[8] Musilek K., Kuca K. and Jun D.: Bioorg. Med. Chem. Lett., 2006, 16, 622.
https://doi.org/10.1016/j.bmcl.2005.10.059

[9] Kuca K., Musilova L., Palecek J. et al.: Molecules, 2009, 14, 4915.
https://doi.org/10.3390/molecules14124915

[10] Mercey G., Renou J., Verdelet T. et al.: J. Med. Chem., 2012, 55, 10791.
https://doi.org/10.1021/jm3015519

[11] Acharya J., Rana H. and Kaushik M.: Eur J. Med. Chem., 2011, 46, 3926.
https://doi.org/10.1016/j.ejmech.2011.05.064

[12] Primozic S., Odzak R., Tomic S. et al.: Med. Chem. Def., 2004, 2, 1.

[13] Reiner E. and Radic Z. Mechanism of Action of Cholinesterase Inhibitors [in:ï E. Giacobini (Ed.), Cholinesterases and Cholinesterase Inhibitors. Martin Dunitz Ltd., London 2000.

[14] Skrinjaric-Spoljar M. and Kralg M.: Arch. Toxicol., 1980, 45, 21.
https://doi.org/10.1007/BF00303291

[15] Gupta B., Sharma R., Singh N. et al.: Arch. Toxicol., 2014, 88, 381.
https://doi.org/10.1007/s00204-013-1136-z