(from Mercey et al.) The best global reactivation efficiency has been obtained with a linker length of four or five carbon atoms attached on position 6 of the pyridine ring,i.e., for 1b and 1c. Their derivatives show a lower ability to reactivate VX-inhibited hAChE, yet superior to that of 2-PAM. three new compounds reported,1d,1e, and 1h, are more efficient than TMB-4 for reactivation of tabun-inhibited AChE, while 1a and 1i are as efficient as TMB-4. 1b-d are as efficient as obidoxime and TMB-4 toward paraoxon-inhibited AChE
Pyridinium and bis-pyridinium aldoximes are used as antidotes to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus nerve agents. Herein, we described a series of nine nonquaternary phenyltetrahydroisoquinoline-pyridinaldoxime conjugates more efficient than or as efficient as pyridinium oximes to reactivate VX-, tabun- and ethyl paraoxon-inhibited human AChE. This study explores the structure-activity relationships of this new family of reactivators and shows that 1b-d are uncharged hAChE reactivators with a broad spectrum.
