N‐(Biphenyl‐3‐ylmethyl)ethanamines as G protein‐biased agonists of 5‐HT7R

There has been much attention to biased ligands of G protein‐coupled receptors (GPCRs) for potential pharmacological benefits. Recently, we reported N‐((6‐chloro‐2'‐methoxy‐[1,1'‐biphenyl]‐3‐yl)methyl)ethanamine 1 as G protein‐biased agonist of 5‐HT7R, which could be used as a chemical pro...

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Veröffentlicht in:Bulletin of the Korean Chemical Society 2022, 43(1), , pp.73-77
Hauptverfasser: Kim, Doyoung, Lee, Jieon, Kwag, Rina, Kim, Hyunbin, Oh, Hyunji, Moon, Bongjin, Kim, Hak Joong, Seong, Jihye, Jeon, Byungsun, Kang, Taek, Choo, Hyunah
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Sprache:eng
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Zusammenfassung:There has been much attention to biased ligands of G protein‐coupled receptors (GPCRs) for potential pharmacological benefits. Recently, we reported N‐((6‐chloro‐2'‐methoxy‐[1,1'‐biphenyl]‐3‐yl)methyl)ethanamine 1 as G protein‐biased agonist of 5‐HT7R, which could be used as a chemical probe for the study on treatment discovery of autism spectrum disorder. Herein, we describe the synthesis of derivatives of the compound 1 and their biological evaluations in both G protein and β‐arrestin signaling pathway. Total 16 compounds were synthesized and evaluated, and the compounds 3c, 3f, 3i, and 3p could be called as G protein‐biased agonists like the compound 1. Among the four compounds, the compound 3c was the best in efficacy with an Emax value of 73% and the compound 3f was the most potent agonist with an EC50 value of 0.094 μM. N‐((6‐chloro‐2'‐methoxy‐[1,1'‐biphenyl]‐3‐yl)methyl)ethanamine 1, an G protein‐biased agonist, was derivatized and among the derivatives of the compound 1, the compounds 3c, 3f, 3i, and 3p were also turned out as G protein‐biased agonists of 5‐HT7R.
ISSN:1229-5949
0253-2964
1229-5949
DOI:10.1002/bkcs.12427