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 quaternization 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.
Hsu
F L
FL
U.S. Army Chemical Research, Development, and Engineering Center, Aberdeen Proving Ground, MD 21010-5423.
Ray
R
R
Clark
O E
OE
Munavalli
S
S
Ashman
W P
WP
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004593:Electrophorus; D008968:Molecular Conformation; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D011726:Pyridinium Compounds