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Enhanced Affinity for 3-Amino-Chromane-Derived ?₁ Receptor Ligands.

ABSTRACT: The ?₁ receptor is implicated in regulating a diverse range of physiology and is a target for developing therapies for cancer, pain management, neural degradation, and COVID-19. This report describes 36 phenethylamine-containing 3-amino-chromane ligands, which bind to ?₁ with low nM affinities. The family consists of 18 distinct compounds and each enantiomer was independently assayed. Three compounds with the greatest affinity bind in the 2 nM K _i range (?8.7 pK _i). Furthermore, ligands with the (3R,4R) absolute stereochemistry on the 3-amino-chromane core have a higher affinity and greater ?₁ versus TMEM97 selectivity. The most promising ligands were assayed in 661W cells, which did not show significant protective effects.

SUBMITTER: Porter MR

PROVIDER: S-EPMC7758967 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Enhanced Affinity for 3-Amino-Chromane-Derived σ1 Receptor Ligands.

Porter Matthew R MR Xiao Haiyan H Maity Sanjay S Vail Nora N Smith Sylvia B SB Topczewski Joseph J JJ

ACS omega 20201211 50

The σ1 receptor is implicated in regulating a diverse range of physiology and is a target for developing therapies for cancer, pain management, neural degradation, and COVID-19. This report describes 36 phenethylamine-containing 3-amino-chromane ligands, which bind to σ1 with low nM affinities. The family consists of 18 distinct compounds and each enantiomer was independently assayed. Three compounds with the greatest affinity bind in the 2 nM K i range (∼ ...[more]

PMID: 33376910

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