Synthesis of Aminoethyl-Substituted Piperidine Derivatives as σ₁ Receptor Ligands with Antiproliferative Properties.

ABSTRACT: A series of novel σ₁ receptor ligands with a 4-(2-aminoethyl)piperidine scaffold was prepared and biologically evaluated. The underlying concept of our project was the improvement of the lipophilic ligand efficiency of previously synthesized potent σ₁ ligands. The key steps of the synthesis comprise the conjugate addition of phenylboronic acid at dihydropyridin-4(1H)-ones 7, homologation of the ketones 8 and introduction of diverse amino moieties and piperidine N-substituents. 1-Methylpiperidines showed particular high σ₁ receptor affinity and selectivity over the σ₂ subtype, whilst piperidines with a proton, a tosyl moiety or an ethyl moiety exhibited considerably lower σ₁ affinity. Molecular dynamics simulations with per-residue bind

SUBMITTER: Holtschulte C 

PROVIDER: S-EPMC9303367 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature