3-Amino-chromanes and Tetrahydroquinolines as Selective 5-HT2B, 5-HT7, or σ1 Receptor Ligands

Matthew R. Porter; Haiyan Xiao; Jing Wang; Sylvia B. Smith; Joseph J. Topczewski

doi:10.1021/acsmedchemlett.9b00225

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

Matthew R. Porter, Haiyan Xiao, Jing Wang, Sylvia B. Smith, Joseph J. Topczewski

Chemistry (Twin Cities)

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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-HT_2B, 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.

Original language	English (US)
Pages (from-to)	1436-1442
Number of pages	7
Journal	ACS Medicinal Chemistry Letters
Volume	10
Issue number	10
DOIs	https://doi.org/10.1021/acsmedchemlett.9b00225
State	Published - Oct 10 2019

Bibliographical note

Funding 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.

Publisher Copyright:
© 2019 American Chemical Society.

Keywords

5-HT
G protein-coupled receptors
neuroprotection
serotonin receptors
σ receptor

Publisher link

10.1021/acsmedchemlett.9b00225

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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.",

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note = "Funding 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. Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

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AU - Wang, Jing

AU - Smith, Sylvia B.

AU - Topczewski, Joseph J.

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