3-Amino-chromanes and Tetrahydroquinolines as Selective 5-HT_2B, 5-HT₇, or σ₁ Receptor Ligands

Abstract

The phenethylamine backbone is a privileged substructure found in a wide variety of G protein-coupled receptor (GPCR) ligands. This includes both endogenous neurotransmitters and active pharmaceutical agents. More than 20 structurally unique heterocyclic phenethylamine derivatives were broadly evaluated for GPCR affinity. Selective ligands for the 5-HT2B, 5-HT7, and σ1 receptors were identified, each with low nanomolar binding affinities. The σ1 receptor affinity was supported in a cellular assay that provided evidence for increased cell survival under oxidative stress.