STABILITY OF MONOBENZYLOXIME AND BISBENZYLOXIME ETHERS OF THE ACETYLCHOLINESTERASE REACTIVATOR TMB-4

Mono-and bisbenzyloxime ethers of the bispyridinium derivative TMB-4 ( UNO, DUG) 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 o xime 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-va lues 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.