Synthesis and biological activity of pyridinium-type acetylcholinesterase inhibitors

A novel series of bispyridinium-type acetylcholinesterase (AChE) inhibitors derived from obidoxime, being active in the lower micromolar range, has been reported recently. According to the hypothesis that shorter pyridinium compounds should exhibit higher activity, a new series of compounds was synthesized that has 2,6-dichlorobenzyl, 2-chlorobenzyl and phthalimidomethyl moieties, respectively, at one end of the molecule and that are systematically shortened from the contralateral end. The concentration inhibiting the AChE and butyrylcholinesterase (BChE) by 50% (IC50) was evaluated by means of Ellman's test. Compounds characterized by a phenylpropyl residue at the contralateral end (3) were found to have IC50 values comparable with tacrine. In addition, the affinity of 3c toward the BChE was lower, indicating a lower degree of side effects.