New oxime reactivators connected with CH2O(CH2)nOCH2 linker and their reactivation potency for organophosphorus agents-inhibited acetylcholinesterase

Yang, Garp Yeol; Oh, Kyung-Ae; Park, No‐Joong; Jung, Young‐Sik

doi:10.1016/j.bmc.2007.08.056

Cited by 51 publications

(14 citation statements)

References 25 publications

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“…The method for the preparation of 3 is described in Scheme 2, and starts with ethylene glycol, converted with paraformaldehyde and hydrogen chloride without solvent, to the dichloro derivative 8 [22]. Compound 8 was subsequently converted into the diacetate 9 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 9,9′-[1,2-Ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, an Impurity of Acyclovir

et al. 2012

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Section: Resultsmentioning

confidence: 99%

Synthesis of 9,9′-[1,2-Ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, an Impurity of Acyclovir

et al. 2012

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“…In the in vitro test of their potency to reactivate AChE inhibited by organophosphorus agents at 5x10 -3 M concentration, the reactivation ability of the oxime 12 was the most potent, and showed reactivation potencies of 63% for HF-AChE inhibited by DFP, 51% for RBC-AChE inhibited by DFP, 67% for HF-AChE inhibited by paraoxon, and 81% for RBC-AChE inhibited by paraoxon [15]. The reactivation potency of 12 was compared with the potency of 2-PAM and HI-6.…”

Section: Reactivation Potencymentioning

confidence: 98%

“…at 45 o C for 20 h. Similarly the other oximes (14,15) were prepared by the reaction of 5 or 7 with 17 in DMF at r.t. for 24 h.…”

Section: Chemistrymentioning

confidence: 99%

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Current Study on the Development of Bis-pyridinium Oxime Reactivators for the Antidotal Treatment of Poisoning by Toxic Organophosphorus Agents

Kuca¹

2011

COC

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A number of oxime reactivators have been synthesized and studied for the antidotal treatment of poisoning by toxic organophosphorus agents, and several oximes are currently available to reactivate the organophosphorus agents-induced acetylcholinesterase inhibition. However, there is no oxime with broad spectrum suitable for the antidotal treatment of poisoning with various organoposphorus warfare agents as well as insecticides. In addition, current available oximes have very limited brain-blood barrier (BBB) penetration, even though hydrophobic toxic organophosphorus agents can easily penetrate BBB. Therefore, the development of BBB permeable oxime reactivators is one of great challenges in these days. In this review, we summarize advances in the synthesis and reactivation evaluation of oximes that have been studied in our research group. Various approaches have been employed to design these analogs; for example, bispyridinium oximes with (CH2)2O(CH2)2 linkers, (CH2)O(CH2)nO(CH2) linkers and (CH2)n linkers as well as fluorinated bis-pyridinium oximes.

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“…Oxime 290 showed increased reactivation ability of HF AChE, while oxime 291 was the best reactivator of BE AChE. 90 Furthermore, the same group tested various non-quaternary, monoquaternary, and bisquaternary oximes (288-289, 293-299; Figs. 26 and 27).…”

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Design, evaluation and structure—Activity relationship studies of the AChE reactivators against organophosphorus pesticides

Musílek

Doležal

Gunn‐Moore

et al. 2011

Medicinal Research Reviews

113

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Organophosphate pesticides (OPPs; e.g. chlorpyrifos, diazinon, paraoxon) are a wide and heterogeneous group of organophosphorus compounds. Their biological activity of inhibiting acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) ranks them as life endangering agents. The necessary treatment after OPP exposure involves the use of parasympatolytics (e.g. atropine), oxime reactivators (e.g. obidoxime), and anticonvulsive drugs (e.g. diazepam). Therefore, the reactivators of AChE are essential compounds in the treatment of OPP intoxications. Commercial AChE reactivators (e.g. pralidoxime, HI-6, obidoxime, trimedoxime, methoxime) were originally developed for other members of the organophosphate family, such as nerve agents (e.g. sarin, soman, tabun, VX). Pralidoxime, HI-6, and methoxime were found to be weak reactivators of OPP-inhibited AChE. Obidoxime and trimedoxime showed satisfactory reactivation against various OPPs with minor toxicity issues. During the last two decades, the treatment of OPP exposure has become more widely discussed because of growing agricultural production, industrialization, and harmful social issues (e.g. suicides). In this review is the summarized design, evaluation, and structure-activity relationship studies of recently produced AChE reactivators. Since pralidoxime, over 300 oximes have been produced or tested against OPP poisoning, and several novel compounds show very promising abilities as comparable (or higher) to commercial oximes. Some of these are highlighted for their further testing of OPP exposure and, additionally, the main structure-activity relationship of AChE reactivators against OPP is discussed.

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New oxime reactivators connected with CH2O(CH2)nOCH2 linker and their reactivation potency for organophosphorus agents-inhibited acetylcholinesterase

Cited by 51 publications

References 25 publications

Synthesis of 9,9′-[1,2-Ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, an Impurity of Acyclovir

Synthesis of 9,9′-[1,2-Ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, an Impurity of Acyclovir

Current Study on the Development of Bis-pyridinium Oxime Reactivators for the Antidotal Treatment of Poisoning by Toxic Organophosphorus Agents

Design, evaluation and structure—Activity relationship studies of the AChE reactivators against organophosphorus pesticides

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