The Design, Synthesis and Screening of Potential Pyridinium Oxime Prodrugs

Abstract

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-PAM's) 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.

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Document Details

Document Type
Technical Report
Publication Date
Sep 30, 1985
Accession Number
ADA184481

Entities

People

  • Ronald T. Borchardt

Organizations

  • University of Kansas

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  • Biomedical

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  • Biomedical Research
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Fields of Study

  • Chemistry

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  • Neurotoxicology
  • Polymer Science and Technology

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  • Microelectronics