Bridged Bicyclic Oximes as Acetylcholinesterase Reactivators
Annual rept. (Final) 15 Apr 1983-30 Jun 1985
ILLINOIS UNIV AT CHICAGO CIRCLE DEPT OFCHEMISTRY
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In our search for novel acetylcholinesterase reactivators, we have synthesized a number of 8-azabicyclo oximes, 1-phenyl-3-aminopropane oximes, phenylpiperidino oximes and simple pyridinium oximes. Particularly interesting are a-hydroxy oximes, for which a new synthetic method was developed. Our design concept for reactivator molecules focuses on naturally cholinergic molecules which have a binding affinity for the catalytic site on the enzyme. Incorporation of an oximino group in a molecule with an inherent affinity for the active site should lead to effective reactivation. This has been demonstrated for tropyl systems. An X-ray structure determination on a member of this class, namely, 2a-hydroxy-3-tropanone oxime methiodide has been carried out. Two sensitive assay procedures have been devised and used in our work for following the reactivation of acetylcholinesterase that has been inhibited by diisopropylfluoro-phosphonate DFP.
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