- Synthesis and in vitro evaluation of neutral aryloximes as reactivators of Electrophorus eel acetylcholinesterase inhibited by NEMP, a VX surrogate
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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.
- Cavalcante, Samir F. de A.,Kitagawa, Daniel A.S.,Rodrigues, Rafael B.,Bernardo, Leandro B.,da Silva, Thiago N.,dos Santos, Wellington V.,Correa, Ana Beatriz de A.,de Almeida, Joyce S.F.D.,Fran?a, Tanos C.C.,Ku?a, Kamil,Simas, Alessandro B.C.
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- Bis-methylene ether pyridinium compound preparation
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An illustrative embodiment of the invention substitutes solid, non-carcinogenic bis(methanesulfonoxymethyl) ether for bis-chloromethyl ether in a low temperature reaction of about 0°-5° C. for the production of bis-methylene ether pyridinium quaternary compounds. In this way, the production of important nerve agent antidotes (toxogonin, HI-6 and HGG-12) by a method of synthesis using the reactant bis-mesylmethyl ether, is carried out in appreciably greater safety.
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- Alkylating agents and method of use thereof
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The present invention comprises a haloacetoxyalkyl ether having the formula: STR1 wherein R is H or a C1 -C4 substituted or unsubstituted alkyl group, R' is H or a C1 -C3 group, and X is chlorine or fluorine; aroyloxymethyl ethers having the formula: wherein the R is p-NO2 C6 H4, halogen substituted C6 H4, or other aromatics; the method of making such ethers and monoquaternary salts; and the method of alkylating amines, pyridines, or acetals or pyridine derivatives with such ethers to form quaternary ammonium salts; particularly HI-6, HGG-12, Toxogonin, and SAS-128.
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