AUTHOR=Wang Danhui , Zhao Wenjie , Zhang Zuzhi , Zhang Yanchun , Li Jiaming , Huang Weijun 

TITLE=Design, synthesis and biological evaluation of novel biphenylsulfonamide derivatives as selective AT2 receptor antagonists

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.984717

DOI=10.3389/fchem.2022.984717

ISSN=2296-2646

ABSTRACT=<p>A novel series of benzenesulfonamide derivatives that selectively act on the AT<sub>2</sub> receptor have been designed and synthesized. The binding affinity and functional activity were evaluated by radio-ligand binding analysis and cell neurite outgrowth assay, respectively. The compounds <bold>8d</bold>, <bold>8h</bold>, <bold>8i</bold>, <bold>8j</bold>, <bold>8l</bold>, and <bold>9h</bold> exhibited moderate selectivity and affinity for the AT<sub>2</sub> receptor. Among them, <bold>8j</bold> exhibited agonist activity and <bold>8l</bold> displayed similar selectivity to the AT<sub>2</sub> receptor with <bold>PD123,319</bold>. Molecular docking was carried out to analyze the binding mode and binding site between the compound and the AT<sub>2</sub> receptor to provide a reference for further development.</p>