Novel Heterobivalent Tacrine Derivatives as Cholinesterase Inhibitors with Notable Selectivity Toward Butyrylcholinesterase
journal contributionposted on 14.12.2006, 00:00 by Paul W. Elsinghorst, Camino M. González Tanarro, Michael Gütschow
Two series of novel heterobivalent tacrine derivatives were synthesized. A trimethoxy substituted benzene was linked to the tacrine moiety by a hydrazide-based linker. The compounds were evaluated as cholinesterase inhibitors, and trimethoxybenzoic acid derivatives with 11- or 12-atom spacers were the most potent inhibitors of human acetylcholinesterase. The inhibitors showed a surprising selectivity toward human butyrylcholinesterase, where several trimethoxyphenylpropionic acid derivatives had IC50 values less than 250 pM.