Accession Number : ADA184479

Title :   The Design, Synthesis and Screening of Potential Pyridinium Oxime Prodrugs.

Descriptive Note : Annual rept. 1 Mar 84-31 Jul 85,

Corporate Author : KANSAS UNIV LAWRENCE CENTER FOR BIOMEDICAL RESEARCH

Personal Author(s) : Borchardt,Ronald T

PDF Url : ADA184479

Report Date : 31 Jul 1985

Pagination or Media Count : 54

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.

Descriptors :   *OXIMES, ORGANOPHOSPHATES, ACETYLCHOLINESTERASE, ANALOGS, SYNTHESIS(CHEMISTRY), BIOASSAY, NEUROCHEMISTRY, CENTRAL NERVOUS SYSTEM, REGENERATION(PHYSIOLOGY), ENZYME PRECURSORS, LIPOPHILIA, PHARMACOLOGY, NEUROCHEMICAL TRANSMISSION, METHYL RADICALS, CHLORINE, BROMINE, LIQUID CHROMATOGRAPHY

Subject Categories : Pharmacology
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE