Preparation and testing of bisquarternary pyridinium reactivators of acetylcholinesterase

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Hana Leblochová Consultant Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Thesis Preparation and testing of bisquarternary pyridinium reactivators of acetylcholinesterase Within this rigorous thesis, 21 new potential bisquarternary pyridinium AChE reactivators were prepared and their reactivation abilities on dichlorvos and paraoxon inhibited AChE were determined in vitro. Pralidoxime (2-PAM), obidoxime, asoxime (HI-6), trimedoxime (TMB-4), methoxime (MMC), K027 and K203 were used as reference compounds as they are known to be able to partially reactivate paraoxon and dichlorvos inhibited AChE. The experimental data showed that 6 compounds were able to achieve reactivation parameters recommended for in vivo testing on dichlorvos inhibited hAChE and 8 compounds on paraoxon inhibited hAChE. The compounds (9), (19), (20) and (21) seem to be very promising reactivators since they were able to reactivate hAChE inhibited by both pesticides. Based on in vitro results the structure activity relationships for newly prepared compounds were determined. Compounds having an oxime group in the 2- and 4- position to the pyridinium ring, the 1,4-phenyldimethylenyl or...