title: Stability of mono- and bisbenzyloxime ethers of the acetylcholinesterase reactivator TMB-4.
abstract: Mono- and bisbenzyloxime ethers of the bispyridinium derivative TMB-4 (UNO, DUO) are potent allosteric modulators of the muscarinic receptor attracting clinical interest in case of organophosphate poisoning. In order to work out the stability of these compounds oximes, different oxime ethers and potential degradation products were synthesized and UV- and NMR-spectroscopically characterized. The process of degradation of all compounds was observed under stress conditions at varying pH-values and different temperatures by means of time-dependent NMR- und UV-measurements. The pyridinium aldoxime turned out to be rather stable, whereas the oxime ether and cyano derivatives convert to the pyridone at high pH-values and high temperature. The mechanism of degradation is discussed.
authors.affiliation: Pharmazeutisches Institut, Universität Bonn, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Inkmann
authors.forename: U
authors.initials: U
authors.lastname: Holzgrabe
authors.forename: K F
authors.initials: KF
authors.lastname: Hesse
mesh_terms: D002801:Cholinesterase Reactivators / Q000737:chemistry*; D003460:Crystallization; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D014289:Trimedoxime / Q000737:chemistry*
chemical_list: D002801:Cholinesterase Reactivators; D014289:Trimedoxime