Casualties caused by nerve agents, potent acetylcholinesterase inhibitors, have attracted attention from media recently. Poisoning with these chemicals may be fatal if not correctly addressed. Therefore, research on novel antidotes is clearly warranted. Pyridinium oximes are the only clinically available compounds, but poor penetration into the blood-brain barrier hampers efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in SAR studies, we synthesized and evaluated neutral aryloximes as reactivators for acetylcholinesterase inhibited by NEMP, a VX surrogate. Although few tested compounds reached comparable reactivation results with clinical standards, they may be considered as leads for further optimization.

Brazilian Army Institute of Chemical Biological Radiological and Nuclear Defense Avenida das Américas 28705 Rio de Janeiro 23020 470 Brazil

Brazilian Army Institute of Chemical Biological Radiological and Nuclear Defense School of Pharmacy Avenida Santa Cruz 1631 Rio de Janeiro 21710 255 Brazil; Department of Chemistry Faculty of Science University of Hradec Králové Rokitanskeho 62 50003 Hradec Králové Czech Republic

Department of Chemistry Faculty of Science University of Hradec Králové Rokitanskeho 62 50003 Hradec Králové Czech Republic

Department of Chemistry Faculty of Science University of Hradec Králové Rokitanskeho 62 50003 Hradec Králové Czech Republic; Laboratory of Molecular Modelling Applied to Chemical and Biological Defense Praça General Tibúrcio 80 Rio de Janeiro 22290 270 Brazil

Emergency and Rescue Department School of Biomedicine Rua Marquês de Abrantes 55 Rio de Janeiro 22230 060 Brazil

Laboratory of Molecular Modelling Applied to Chemical and Biological Defense Praça General Tibúrcio 80 Rio de Janeiro 22290 270 Brazil

University Castelo Branco School of Pharmacy Avenida Santa Cruz 1631 Rio de Janeiro 21710 255 Brazil

Walter Mors Institute of Research on Natural Products CCS Bloco H Rio de Janeiro 21941 902 Brazil

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