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.
|Number of pages||5|
|Journal||Bulletin of the Korean Chemical Society|
|Publication status||Published - 2022 Jan|
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