Development of New Benzylpiperazine Derivatives as σ₁ Receptor Ligands with in Vivo Antinociceptive and Anti-Allodynic Effects.

ABSTRACT: σ-1 receptors (σ₁R) modulate nociceptive signaling, driving the search for selective antagonists to take advantage of this promising target to treat pain. In this study, a new series of benzylpiperazinyl derivatives has been designed, synthesized, and characterized for their affinities toward σ₁R and selectivity over the σ-2 receptor (σ₂R). Notably, 3-cyclohexyl-1-{4-[(4-methoxyphenyl)methyl]piperazin-1-yl}propan-1-one (15) showed the highest σ₁R receptor affinity (K_i σ₁ = 1.6 nM) among the series with a significant improvement of the σ₁R selectivity (K_i σ₂/K_i σ₁ = 886) compared to the lead compound 8 (K_i σ

SUBMITTER: Romeo G 

PROVIDER: S-EPMC8291485 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature