The Design, Synthesis and Screening of Potential Pyridinium Oxime Prodrugs
Final rept. 1 Mar 1982-31 Jul 1985
KANSAS UNIV LAWRENCE CENTER FOR BIOMEDICAL RESEARCH
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In an attempt to improve the delivery of quaternary pyridinium oxime regenerators of acetylcholinesterase AChE to the central nervous system CNS, structural analogs and prodrugs of N-methylpyridinium 2-carbaldoxime 2-PAM have been synthesized. The potential prodrugs are dihydropyridinium oximes pro- 2-PAMs or tetrahydropyridinium oximes, which possess electron-withdrawing substituents in the 3- or 5-position. As precursors to these prodrugs, we have synthesized and characterized a series of 5-substituted-2-PAMs I, Br, Cl, CH, CN, CONH2-substituted and a series of 3-substituted PAMs I, Br, Cl, CH3- substituted. These analogs were tested in vitro for their ability to reactivate diisopropylfluorophosphate DEP-inactivated eel AChE.