Design of a potent reactivator of tabun-inhibited acetylcholinesterase--synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203).
Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Among the organophosphates, with the exception of soman, tabun (GA) intoxications are the least responsive to treatment with commercially available therapeutics. A rational design was used to increase reactivation ability and decrease the toxicity of the novel reactivator. (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203) has better properties than previously tested compounds in vitro and, therefore, is a potential candidate for the treatment of GA intoxication in vivo.
Musilek
Kamil
K
Department of Toxicology, Faculty of Military Health Sciences, University of Defense, Hradec Kralove, CZ.
Jun
Daniel
D
Cabal
Jiri
J
Kassa
Jiri
J
Gunn-Moore
Frank
F
Kuca
Kamil
K
D000110:Acetylcholinesterase / Q000737:chemistry*; D002619:Chemical Warfare Agents / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D007700:Kinetics; D010755:Organophosphates / Q000737:chemistry*; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; C009374:tabun