Author/Authors :
Simon J. Mantell، نويسنده , , Peter T. Stephenson، نويسنده , , Sandra M. Monaghan، نويسنده , , Graham N. Maw، نويسنده , , Michael A. Trevethick، نويسنده , , Michael Yeadon، نويسنده , , Ruth F. Keir، نويسنده , , Don K. Walker، نويسنده , , Rhys M. Jones، نويسنده , , Matthew D. Selby، نويسنده , , David V. Batchelor، نويسنده , , Stuart Rozze، نويسنده , , Helene Chavaroche، نويسنده , , Tim J. Hobson، نويسنده , , Peter G. Dodd، نويسنده , , Arnaud Lemaitre، نويسنده , , Karen N. Wright، نويسنده , , Emilio F. Stuart، نويسنده ,
Abstract :
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.
Keywords :
Clearance , Cmax , Chronic bronchitis , neutrophil , inhalation
