کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1314574 | 975975 | 2011 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis of some fluorine-containing pyridinealdoximes of potential use for the treatment of organophosphorus nerve-agent poisoning Synthesis of some fluorine-containing pyridinealdoximes of potential use for the treatment of organophosphorus nerve-agent poisoning](/preview/png/1314574.png)
Fluoroheterocyclic aldoximes were screened as therapeutic agents for the treatment of anticholinesterase poisoning. 2-Fluoropyridine-3- and -6-aldoxime, and 3-fluoropyridine-2- and -4-aldoxime, were synthesised. Attempts to obtain 3,5,6-trifluoropyridine-2,4-bis(aldoxime) and -2-aldoxime, however, proved unsuccessful. Pentafluorobenzaldoxime was prepared by oximation of pentafluorobenzaldehyde. Acid dissociation constants (pKa) and second-order rate constants (kox−) of the fluorinated pyridinealdoximes towards sarin were measured. 2,3,5,6-Tetrafluoropyridine-4-aldoxime had the best profile: its kox− approached that of the therapeutic oxime P2S (310 vs. 120 l mol−1 min−1), but its higher pKa (9.1 vs. 7.8) fell short of the target figure of 8 required for reactivation of inhibited acetylcholinesterase in vivo. N-alkylation of the fluorinated pyridine-aldoximes may reduce their pKa nearer to 8 and enhance their therapeutic potential.
Acid dissociation constants (pKa) and second-order rate constants towards sarin (kox− were compared to those of the oxime P2S.Figure optionsDownload as PowerPoint slideHighlights
► 2-Fluoropyridine-3- and -6-aldoxime, 3-fluoropyridine-2- and -4-aldoxime, isolated.
► pKa and second-order rate constants towards sarin measured.
► 2,3,5,6-Tetrafluoropyridine-4-aldoxime had the best profile.
► N-alkylation may reduce pKa nearer to 8 and enhance therapeutic potential.
Journal: Journal of Fluorine Chemistry - Volume 132, Issue 8, August 2011, Pages 541–547