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

  • Bioorg Med Chem Lett. 2008 Feb 15;18(4):1284-7. doi: 10.1016/j.bmcl.2008.01.033.
Simon J Mantell  1 ,  Peter T Stephenson ,  Sandra M Monaghan ,  Graham N Maw ,  Michael A Trevethick ,  Michael Yeadon ,  Ruth F Keir ,  Don K Walker ,  Rhys M Jones ,  Matthew D Selby ,  David V Batchelor ,  Stuart Rozze ,  Helene Chavaroche ,  Tim J Hobson ,  Peter G Dodd ,  Arnaud Lemaitre ,  Karen N Wright ,  Emilio F Stuart
Affiliations
  • 1. Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Kent CT13 9NJ, United Kingdom.
PMID: 18243699 DOI: 10.1016/j.bmcl.2008.01.033
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.