2-{<i>N</i>-[ω-(1-Benzylpiperidin-4-yl)alkyl]amino}-6-[(prop-2-yn-1-yl)amino]pyridine-3,5-dicarbonitriles Showing High Affinity for σ_1/2 Receptors.

ABSTRACT: Sigma receptors (σRs) represent very attractive biological targets for the development of potential agents for the treatment of several neurological disorders. In the search for new small molecule drugs against neuropathic pain, we identified 2-{[2-(1-benzylpiperidin-4-yl)ethyl]amino}-6-[methyl(prop-2-yn-1-yl)amino]pyridine-3,5-dicarbonitrile (5) as a polyfunctionalized small pyridine with potent dual-target activities against acetylcholinesterase (AChE) (IC₅₀ = 13 nM) and butyrylcholinesterase (BuChE) (IC₅₀ = 3.1 µM), exhibiting high σ₁R affinity (K_i(hσ₁R) = 1.45 nM) and 290-fold selectivity over the σ₂R subtype. These results are in good agreement with those found in the molecular modeling of compound 5

SUBMITTER: Deuther-Conrad W 

PROVIDER: S-EPMC11818082 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature