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1Sar of A Series of Inhaled A(2a) Agonists and Comparison of Inhaled Pharmacokinetics in A Preclinical Model with Clinical Pharmacokinetic Data

Simon J. Mantell,Peter T. Stephenson,Sandra M. Monaghan,Graham N. Maw,Michael A. Trevethick,Michael Yeadon,Don K. Walker,Matthew D. Selby,David V. Batchelor,Stuart Rozze,Helene Chavaroche,Arnaud Lemaitre,

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. The pharmacological and pharmacokinetic SAR of a series of inhaled A(2A) agonists is described leading through to human pharmacokinetic data for a clinical candidate.

2009BIOORGANIC & MEDICINAL CHEMISTRY LETTERS（2009）引用：32

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2Inhaled Adenosine A2A Receptor Agonists for the Treatment of Chronic Obstructive Pulmonary Disease

Simon J. Mantell,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,

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.

2008BIOORGANIC & MEDICINAL CHEMISTRY LETTERS（2008）引用：27

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3Nicotinamide derivatives and a tiotropium salt in combination for the treatment of e.g. inflammatory, allergic and respiratory diseases