Anticholinesterase Therapeutics

摘要

A total of 50 new experimental therapeutics for treatment or pretreatment of OPnerve agent intoxication were prepared, characterized, and submitted to WRAIR for biological evaluation. Most of these materials are quaternary 1,2,3,-(trisubstituted) imidazolium salts. Although several new side-chain substituents were investigated in the quaternary imidazolium system, none showed any significant improvement over previously identified substituents in ability to enhance the therapeutic value of the imidazolium compounds against soman in the mouse, either in treatment or pretreatment mode of administration. Investigation of several new nonoxime analogs of aome previously identified efficacious imidazolium oximes revealed that methyl remains the best substituent for therapeutic effectiveness at the imidazolium C2 position. Several new quaternary 1,2,3,-(trisubstituted)imidazolium salts were identified as potential leads for future development work. Additionally, some novel bicyclic, conformationally constrained derivatives of some earlier, highly effective quaternary imidazolium salts were prepared, characterized, and delivered to WRAIR for biological tests. Anticholinesterase, treatment, pretreatment, soman, therapeutic organophosphorus, nerve agent, RAV.