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

Doyoung Kim, Jieon Lee, Rina Kwag, Hyunbin Kim, Hyunji Oh, Bongjin Moon, Hak Joong Kim, Jihye Seong, Byungsun Jeon, Taek Kang, Hyunah Choo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalBulletin of the Korean Chemical Society
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • 5-HTR
  • autism
  • G protein-biased ligand
  • partial agonist
  • serotonin receptor

ASJC Scopus subject areas

  • Chemistry(all)

Fingerprint

Dive into the research topics of 'N-(Biphenyl-3-ylmethyl)ethanamines as G protein-biased agonists of 5-HT<sub>7</sub>R'. Together they form a unique fingerprint.

Cite this