8-Hydroxyquinolin-2(1H)-one analogues as potential ß2-agonists: Design, synthesis and activity study.

ß2-Agonists that bind to plasmalemmal ß2-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 ß2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50 < 20 pM) and selective ß2-agonists among the compounds tested. They behaved as partial ß2-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 ß2-agonists with potential applicability in chronic respiratory diseases.