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 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).
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Wen-Jun
WJ
Shan
Ling
L
Huang
Qi
Q
Zhou
Huai-Lei
HL
Jiang
Zong-Hua
ZH
Luo
Ke-fang
KF
Lai
Xing-Shu
XS
Li
D058666:Adrenergic beta-2 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D015195:Drug Design; D006168:Guinea Pigs; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D014132:Trachea / Q000187:drug effects*
D058666:Adrenergic beta-2 Receptor Agonists; D058988:Phosphodiesterase 4 Inhibitors