Dual‐Acting Diether Derivatives of Piperidine and Homopiperidine with Histamine H₃ Receptor Antagonistic and Anticholinesterase Activity

Abstract

The study presents novel biological properties of diether derivatives of homo- or substituted piperidine ligands of the histamine H(3) receptor. The compounds were evaluated for their inhibitory potency against acetylcholinesterase (AChE) from the electric eel and butyrylcholinesterase (BuChE) from horse serum. The most interesting multifunctional compound 13 displayed high affinity for the cloned hH(3) R (K(i) = 3.48 nM) and moderate inhibitory potency against both enzymes (IC(50) AChE = 7.91 µM and BuChE = 4.97 µM). Molecular modeling studies revealed interactions with key amino acid residues in the homology model of histamine H(3) receptor ligands, as well as the binding model for AChE and BuChE in the catalytic and peripheral active sites.