Phenyltetrahydroisoquinoline–Pyridinaldoxime Conjugates as Efficient Uncharged Reactivators for the Dephosphylation of Inhibited Human Acetylcholinesterase

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.