Asoxime chloride

Asoxime chloride
Clinical data
Routes of
administration		Intramuscular injection
ATC code
  • none
Legal status
Legal status
  • Experimental
Identifiers
  • 4-carbamoyl-1-[({2-[(E)-(hydroxyimino)methyl]pyridinium-1-yl}methoxy)methyl]pyridinium dichloride
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H16Cl2N4O3
Molar mass359.21 g·mol−1
3D model (JSmol)
  • C1=CC=[N+](C(=C1)/C=N/O)COC[N+]2=CC=C(C=C2)C(=O)N.[Cl-].[Cl-]
  • InChI=1S/C14H14N4O3.2ClH/c15-14(19)12-4-7-17(8-5-12)10-21-11-18-6-2-1-3-13(18)9-16-20;;/h1-9H,10-11H2,(H-,15,19);2*1H checkY
  • Key:QELSIJXWEROXOE-UHFFFAOYSA-N checkY
 X markNcheckY (what is this?)  (verify)

Asoxime chloride, or more commonly HI-6, is a Hagedorn oxime used in the treatment of organophosphate poisoning.

Discovery

HI-6 was developed in the 1968 in Ilse Hagedorn's lab at the University of Freiburg in then West Germany as a potent antidote for poisoning by organophosphorus nerve agents. The compound was created in response to limitations of earlier oxime antidotes, which were effective against some nerve agents but failed to protect against others such as soman.

Structure

Much like pralidoxime, asoxime and other oximes created in the Hagedorn lab (i.e. LüH-6, HLö-7) are pyridine oximes, sharing the same structural feature of a byspyridinium nucleus. Position 2 and 4 on one of the pyridine rings is essential for pharmacological activity, as is position 4 on the second ring for both efficacy and toxic effects alike. Amidation on the second ring at position 4 is essential for reducing toxicity of the derivative compounds.

Position of key groups in Hagedorn Oxime HI-6 (Positions 2 and 4 with respect to the pyridine ring derive most potency, while the amide group in Position two (red) decreases toxicity of HI-6

See also

References

  1. ↑ Cochran R, Kalisiak J, Küçükkilinç T, Radic Z, Garcia E, Zhang L, et al. (August 2011). "Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that resist aging". The Journal of Biological Chemistry. 286 (34): 29718–24. doi:10.1074/jbc.M111.264739. PMC 3191013. PMID 21730071.
  2. ↑ Peter Eyer (20 April 2007). "In memory of Ilse Hagedorn". Toxicology. 233 (1–3). Elsevier: 3–7. doi:10.1016/j.tox.2006.09.014.
  3. ↑ Franz Worek, Peter A. Eyer (2007). Chemical Warfare Agents: Toxicology and Treatment. Chapter 15: Wiley. p. 305-329. doi:10.1002/9780470060032. ISBN 9780470060032.{{cite book}}: CS1 maint: location (link)
  4. ↑ K Schoene, H Oldiges (1970). "Pyridinium- und Imidazoliumsalze als Antidote gegenüber Soman- und Paraoxonvergiftungen bei Mäusen". Archiv für Toxikologie. 26. Springer Nature: 293–305. doi:10.1007/BF00577721.
  5. ↑ Peter A. Lockwood, John G. Clement (1982). "HI-6, an oxime which is an effective antidote of soman poisoning: A structure-activity study". Toxicology and Applied Pharmacology. 64 (1). Elsevier: 140–146. doi:10.1016/0041-008X(82)90332-5.