Synthesis and anticholinesterase activity of new bispyridinium compounds.

Synthesis of new bis(1‐methylpyridinium) compounds containing a 1,4‐diacetylbenzene linkage between the pyridinium moieties from commercially available 2‐, 3‐, and 4‐picoline precursors was accomplished via metallation, reaction of the picolyllithium with 1,4‐dicyanobenzene, and subsequent quatemization of the resulting bispyridyl compounds. Acetylcholinesterase inhibitory activity was determined colorimetrically with purified electric eel enzyme. Examination of structure—activity relationships indicated that the 3‐substituted pyridinium compound is the most potent isomer, followed by the 2‐substituted isomer, and that the 4‐substituted analogue is the least active.