Bridged Bicyclic Systems as Acetylcholinesterase Reactivator and PretreatmentDrugs

摘要

Eighty-eight oximino 0-carbamoyl derivatives of N-alkyl 3-tropanone have beensynthesized and evaluated in vitro as acetylcholinestemse inhibitors as well as in vivo as pretreatment drugs for mice exposed to various nerve agents. Certain compounds are extremely effective in protecting mice against anticholinergic agents. A detailed kinetic analysis of seven representative analogs was carried out and a correlation between rates of acetylcholinesterase inhibition efficacy and stereochemistry in the in vivo inactivation of acetylcholinesterase was observed. Using chiral azabicyclo 3.2.1 octyl oximes of known configuration we have demonstrated enantioselectivity in the reactivation of phosphorylated AChE. Bridged azabicyclic oxime carbamates, acetylcholinenesterase inhibitors, tropane, phencylidine oxime carbamates, norbornan.