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ID: ALA4340501

Journal: Bioorg Med Chem

Title: Design, synthesis and biological evaluation of 5-(2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one derivatives as potent β2-adrenoceptor agonists.

Authors: Xing G, Pan L, Yi C, Li X, Ge X, Zhao Y, Liu Y, Li J, Woo A, Lin B, Zhang Y, Cheng M.

Abstract: A series of novel β2-adrenoceptor agonists with a 5-(2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one moiety was designed, synthesized and evaluated for biological activity in human embryonic kidney 293 cells and isolated guinea pig trachea. Compounds 9g and (R)-18c exhibited the most excellent β2-adrenoceptor agonistic effects and high β21-selectivity with EC50 values of 36 pM for 9g and 21 pM for (R)-18c. They produced potent airway smooth muscle relaxant effects with fast onset of action and long duration of action in an in vitro guinea pig trachea model of bronchodilation. These results support further development of the two compounds into drug candidates.

CiteXplore: 30392952

DOI: 10.1016/j.bmc.2018.10.043