Influence of the Distance Between Quaternary Nitrogen and Oxime Group on the Reactivation Ability of Oximes – Antidotes Against Nerve Agents

h olinesterase reactivators are a group of drugs originally developed as antidotes for treatment of nerve agent intoxications. Although there are five commercially available members of this group, none is considered to be a universal solution for treatment of intoxication caused by all nerve agents. Due to this, novel drug candidates are searched. To find the most promising antidotes, structure activity studies are conducted. In this contribution, distance between quaternary nitrogen and aldoxime (called oxime) group responsible for the reactivation process is discussed. For this purpose, three structurally different oxime reactivators were tested for their potency to reactivate tabun, sarin, cyclosarin and VX agent-inhibited acetylcholinesterase (A ch E; Ec 3.1.1.7). As resulted, only standard oxime reactivators with oxime group connected to the heteroaromatic ring could be considered as promising Ach E reactivators. Those with oxime group on other aromatic ring or those with quaternary nitrogen excluded from heteroarenium ring did not display any reactivation.