8-Hydroxyquinolin-2(1H)-one analogues as potential β-agonists: Design, synthesis and activity study.

β-Agonists that bind to plasmalemmal β-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-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC < 20 pM) and selective β-agonists among the compounds tested. They behaved as partial β-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-agonists with potential applicability in chronic respiratory diseases.