Inhaled adenosine A(2A) receptor agonists for the treatment of chronic obstructive pulmonary disease.

Abstract

COPD is a major cause of mortality in the western world. A(2A) agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A(2A) 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 A(2A) agonists described. A sevenfold improvement in potency and 150-fold reduction in side-effect liability over the lead compound CGS-21680, were obtained.

DOI: 10.1016/j.bmcl.2008.01.033

Cite this paper

@article{Mantell2008InhaledAA, title={Inhaled adenosine A(2A) receptor agonists for the treatment of chronic obstructive pulmonary disease.}, author={Simon J Mantell and Peter T Stephenson and Sandra M Monaghan and Graham N Maw and Michael A Trevethick and Michael Yeadon and R. Keir and Don K Walker and Rhys M. Jones and Matthew D. Selby and David V J Batchelor and Stuart Rozze and Helene Chavaroche and Tim J Hobson and Peter G Dodd and Arnaud Lemaitre and Karen N. Wright and Emilio F Stuart}, journal={Bioorganic & medicinal chemistry letters}, year={2008}, volume={18 4}, pages={1284-7} }