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Bioorg Med Chem Lett. 2008 Feb 15;18(4):1284-7. doi: 10.1016/j.bmcl.2008.01.033. Epub 2008 Jan 12.

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

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Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Kent CT13 9NJ, United Kingdom.


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.

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