Synthesis and biological evaluation of β2 -adrenoceptor agonists bearing the 2-amino-2-phenylethanol scaffold

European Journal of Medicinal Chemistry
Xinyue GeMaosheng Cheng

Abstract

A new series of β2-adrenoceptor agonists bearing the 2-amino-2-phenylethanol scaffold was synthesized. Evaluation of the compounds using cell assays and an in vitro guinea pig trachea relaxation assay showed that 8-hydroxy-5-(2-hydroxy-1-((4-hydroxyphenethyl)amino)ethyl)quinolin-2(1H)-one (compound 5j) has the best pharmacological profile among all the evaluated compounds. The (S)-isomer of 5j was subsequently found to be the active enantiomer with a promising EC50 value of 1.26 nM in stimulating β2-adrenoceptor-mediated cAMP accumulation and a substantially higher selectivity for the β2 than for the β1 subtype. The putative binding mode of (S)-5j revealed by molecular docking of the β2-adrenoceptor resembles that in agonist binding. Taken together, these results showed that compound (S)-5j is a promising compound worthy of further study for the development of β2-adrenoceptor agonists.

Citations

Dec 19, 2019·Pharmacological Reviews·M G MateraM Cazzola
Jan 16, 2019·Acta Pharmacologica Sinica·Anthony Yiu-Ho WooRui-Ping Xiao
Nov 22, 2020·Organic & Biomolecular Chemistry·Anamarija KneŽevićMarijana Vinković
Dec 16, 2020·Expert Opinion on Therapeutic Patents·Gang XingMaosheng Cheng
Nov 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wan Pyo HongHee Nam Lim
Dec 29, 2020·Journal of Experimental Pharmacology·Robert M Burkes, Ralph J Panos
Nov 21, 2020·Journal of Medicinal Chemistry·Gang XingMao-Sheng Cheng
Jul 18, 2021·European Journal of Medicinal Chemistry·Gang XingMaosheng Cheng

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