Dual β2-adrenoceptor agonists-PDE4 inhibitors for the treatment of asthma and COPD

We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both β2-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC50 = 0.278 μM, which was more potent than phthalazinone, IC50 = 0.520 μM) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC50 = 9.3).

Graphical abstractWe designed and synthesized a novel class of dual pharmacology bronchodilators targeting both β2-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC50 = 0.278 μM, which was more potent than phthalazinone, IC50 = 0.520 μM) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC50 = 9.3).Figure optionsDownload full-size imageDownload as PowerPoint slide