The Design, Synthesis and Screening of Potential Pyridinium Oxime Prodrugs.
Abstract
In an attempt to improve the delivery a quaternary pyridinium oxime regenerators of acetycholinesterase (AChE) to the central nervous system (CNS), structural analogs (I) and potential prodrugs (II) of N-methyl-pyridinium 2-carbaldoxime (2-PAM) have been synthesized. The potential prodrugs are dihydropyridinium oximes (pro-2-PAM's), which posses electron withdrawing substituents in the 3- or 5-position. As precursors to these prodrugs, we have synthesized and characterized this year a series of 5-substituted-2-PAM's (C1, CH3, CN, COHN2 substituted) and a series of 3-substituted-2-PAM's (Br, C1, CH3 substituted). These new analogs and the 5-substituted 2-PAM's (I, Br substituted) and 3-substituted-2-PAM (I substituted) synthesized last year were tested in vitro for their ability to reactivate diisopropylfluorophosphate (DEP)-inactivated AChE, in vivo for their ability to protect mice from a challenge dose (2 X LD50) of DFP and, and in vivo for their ability to protect mice from a challenge dose (2x LD50) of Soman.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 31, 1985
- Accession Number
- ADA184479
Entities
People
- Ronald T. Borchardt
Organizations
- University of Kansas