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.
Bibliographical noteFunding Information:
This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35GM124718. This work was supported by the National Institutes of Health under award number R01EY028103 and the Foundation Fighting Blindness award number TA-NMT-0617–021-AUG.
© 2019 American Chemical Society.
- G protein-coupled receptors
- serotonin receptors
- σ receptor