Inhaled adenosine A2A receptor agonists for the treatment of chronic obstructive pulmonary disease

COPD is a major cause of mortality in the western world. A2A agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A2A agonists dictate that a compound needs to be delivered by inhalation to be therapeutically useful. A strategy of minimizing side-effect liability by maximizing systemic clearance was followed and pharmacological and pharmacokinetic SAR of a series of inhaled A2A agonists described. A sevenfold improvement in potency and 150-fold reduction in side-effect liability over the lead compound CGS-21680, were obtained.

Graphical abstractThe pharmacological and pharmacokinetic SAR of a series of inhaled A2A agonists for the treatment of chronic obstructive pulmonary disease is described.Figure optionsDownload full-size imageDownload as PowerPoint slide