Phenyltetrahydroisoquinoline-pyridinaldoxime conjugates as efficient uncharged reactivators for the dephosphylation of inhibited human acetylcholinesterase

J Med Chem. 2012 Dec 13;55(23):10791-5. doi: 10.1021/jm3015519. Epub 2012 Nov 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholinesterase / drug effects
  • Acetylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / pharmacology*
  • Enzyme Reactivators / pharmacology*
  • Humans
  • Isoquinolines / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Oximes / pharmacology*
  • Phosphorylation


  • Cholinesterase Inhibitors
  • Enzyme Reactivators
  • Isoquinolines
  • Oximes
  • phenyltetrahydroisoquinoline-pyridinaldoxime
  • Acetylcholinesterase