Discovery and computational studies of piperidine/piperazine-based compounds endowed with sigma receptor affinity.

ABSTRACT: Herein, we describe our efforts to identify sigma receptor 1 (S1R) ligands through a screening campaign on our in-house collection of piperidine/piperazine-based compounds. Our investigations led to the discovery of the potent compound 2-[4-(benzyl)-1-piperidin-1-yl]-1-4-(4-phenylpiperazin-1-yl)ethanone (1) with high affinity toward S1R (K_i value of 3.2 nM) that was comparable to reference compound haloperidol (K_i value of 2.5 nM). Functional assay revealed that compound 1 acted as S1R agonist. To decipher the binding mode of this promising S1R ligand as a starting point for further structure-based optimization, we analysed the docking pose by using a S1R-structure derived from cocrystal structures of potent ligands in complex with target protein. The co

SUBMITTER: De Luca L 

PROVIDER: S-EPMC10507793 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature