Dual β2-adrenoceptor agonists-PDE4 inhibitors for the treatment of asthma and COPD.
Shan WJ, Huang L, Zhou Q, Jiang HL, Luo ZH, Lai KF, Li XS.
We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both β(2)-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC(50)=0.278 μM, which was more potent than phthalazinone, IC(50)=0.520 μM) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC(50)=9.3).