Synthesis of Bis‐pyridinium Oxime Antidotes Using Bis(methylsulfonoxymethyl) Ether for Organophosphate Nerve Agents.

Yang, Garp Yeol; Yoon, Joong-Ho; Seong, Churl-Min; Park, No-Sang; Jung, Young‐Sik

doi:10.1002/chin.200408129

Cited by 14 publications

(20 citation statements)

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“…The yields of four former known compounds (6c, 8a-c) are comparable with published data [12][13][14][15]. Unfortunately, this system was not applicable in the case of 2,2 0 -bis(hydroxyiminomethyl)-1,1 0 -(1,3-phenylenedimethyl)-bispyridinium dibromide (6b), where other conditions were used (Scheme 4) [16].…”

Section: Resultssupporting

confidence: 84%

Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

Musílek

Kuča

Jun

et al. 2005

Journal of Enzyme Inhibition and Medicinal Chemistry

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Nine potential AChE reactivators were synthesized using a modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by insecticide chlorpyrifos was tested in vitro. 2,2'-Bis(hydroxyiminomethyl)-1,1'-(1,4-phenylenedimethyl)-bispyridinium dibromide seems to be the most potent AChE reactivator. The reactivation potency of these compounds depends on structural factors such as length of the linking chain between both pyridinium rings and position of the oxime moiety on the pyridinium ring.

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Section: Resultssupporting

confidence: 84%

Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

Musílek

Kuča

Jun

et al. 2005

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Pralidoxime and obidoxime were purchased from Léciva (Czech Republic) from Merck (Germany). H-oxime HI-6 was synthesized by Dr Bielavsky earlier at our department, using a standard synthetic approach (Yang et al, 2003). The respective chemical structures are given in figure 1.…”

Section: Chemicalsmentioning

confidence: 99%

Reactivation of organophosphate-inhibited acetylcholinesterase by quaternary pyridinium aldoximes

et al. 2004

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We investigated the relationship between the chemical structure of acetylcholinesterase (AChE; EC 3.1.1.7) reactivators and their potency in reactivating this enzyme, after prior inhibition by VX (O-ethyl-S-(2-diisopropylaminoethyl)-methylthiophosphonate), tabun, sarin, and cyclosarin. The oximes, pralidoxime (2-PAM), HI-6 [1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxa-propane dichloride], obidoxime and HS-6 [1-(2-hydroxyiminomethylpyridinium)-3-(3-carbamoylpyridinium)-2-oxa-propane dichloride] were used as representatives of the group of AChE reactivators. Rat brain AChE was used as the appropriate source of the enzyme. Our results confirm that there is no single broad-spectrum oxime suitable for the treatment of poisoning with all highly toxic organophosphorus agents.

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“…Unfortunately, this approach only protects against a few LD 50 nerve agents [19]. If the amount of nerve agents exceeds the tolerable dose, AChE reactivators (as the causal antidotes) are still required, and so the development of new and more potent AChE reactivators continues [20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Reactivation of sarin-inhibited pig brain acetylcholinesterase using oxime antidotes

Kuča

Jun

2006

J. Med. Toxicol.

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Introduction: Organophosphorus nerve agents inhibit the enzyme, acetylcholinesterase (AChE; EC 3.1.1.7). AChE reactivators (also known as oximes) are generally used for the reactivation of an inhibited enzyme.Methods: Two new AChE reactivators-K033 and K027-were tested for their in vitro reactivation of sarin-inhibited pig-brain AChE. Their reactivation potencies were compared with the commercially available AChE reactivators, pralidoxime, obidoxime, and HI-6.Results: Of the oximes tested, the newly developed oxime K027 achieved the highest reactivation potency (100%; concentration of the oxime −10 −2 M). However, oxime HI-6 (33%) and obidoxime (23%) seem to be the best AChE reactivators for human relevant doses (10 −4 M and lower).Conclusion: For human relevant doses, newly developed oximes (K027 and K033) do not surpass the reactivation potency of the most promising oxime, HI-6.

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Synthesis of Bis‐pyridinium Oxime Antidotes Using Bis(methylsulfonoxymethyl) Ether for Organophosphate Nerve Agents.

Cited by 14 publications

References 1 publication

Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

Reactivation of organophosphate-inhibited acetylcholinesterase by quaternary pyridinium aldoximes

Reactivation of sarin-inhibited pig brain acetylcholinesterase using oxime antidotes

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