8-Hydroxyquinolin-2(1H)-one analogues as potential β<sub>2</sub>-agonists: Design, synthesis and activity study.
Xing G, Zhi Z, Yi C, Zou J, Jing X, Yiu-Ho Woo A, Lin B, Pan L, Zhang Y, Cheng M.
β<sub>2</sub>-Agonists that bind to plasmalemmal β<sub>2</sub>-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β<sub>2</sub>-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC<sub>50</sub> < 20 pM) and selective β<sub>2</sub>-agonists among the compounds tested. They behaved as partial β<sub>2</sub>-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β<sub>2</sub>-agonists with potential applicability in chronic respiratory diseases.