- Synthesis of some fluorine-containing pyridinealdoximes of potential use for the treatment of organophosphorus nerve-agent poisoning
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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 pK a nearer to 8 and enhance their therapeutic potential. Crown Copyright
- Timperley, Christopher M.,Banks, R. Eric,Young, Ian M.,Haszeldine, Robert N.
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p. 541 - 547
(2011/09/15)
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- Synthesis of difluorinated pyridinecarboxaldehyde via electrophilic fluorination
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An efficient synthesis of novel 3,5-difluoropyridine-4-carboxaldehyde using N-fluoro-benzenesulfonimide (NSFi) is described. Difluorination was achieved through the reaction of 3,5-dihalo-1,3-dioxolane pyridine with n-butyllithium followed by N-fluorobenzenesulfonimide at -120 °C in good to high yields. Maintaining the low temperature during the transmetallation was found to be critical for the selective formation of the difluoro-susbstitution over the monofluoro one.
- Ko, Yoon-Joo,Park, Kyung-Bae,Shim, Seung-Bo,Shin, Jung-Hyu
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p. 755 - 759
(2008/03/28)
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- Synthesis of tetrakis(multifluoro-4-pyridyl)porphin derivatives as acetylcholinesterase inhibitors
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New tetrakis(multifluoro-4-pyridyl)porphin derivatives (2-4) and water soluble porphyrin (5) were synthesized to investigate their interactions with acetylcholinesterase from electric eel. These compounds have been found to be the potent reversible inhibitors of the enzyme with K(i) values of μM range. In addition, porphyrin (5) showed broad spectrum of anticancer activities. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Moon, Sin Chul,Shin, Jung-Hyu,Jeong, Bong Ho,Kim, Hee Seok,Yu, Byung Soo,Lee, Ji-Sook,Lee, Bang Sook,Namgoong, Sung Keon
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p. 1435 - 1438
(2007/10/03)
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