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

ACS Med Chem Lett. 2019 Sep 23;10(10):1436-1442. doi: 10.1021/acsmedchemlett.9b00225. eCollection 2019 Oct 10.

Authors

Matthew R Porter¹, Haiyan Xiao^{2

3}, Jing Wang^{2

3}, Sylvia B Smith^{2

3

4}, Joseph J Topczewski¹

Affiliations

¹ Department of Chemistry, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, United States.
² Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia 30912, United States.
³ James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia 30912, United States.
⁴ Department of Ophthalmology, Medical College of Georgia at Augusta University, Augusta, Georgia 30912, United States.

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.

Abstract

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