SAR of a series of inhaled A(2A) agonists and comparison of inhaled pharmacokinetics in a preclinical model with clinical pharmacokinetic data

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4471-5. doi: 10.1016/j.bmcl.2009.05.027. Epub 2009 May 12.

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. 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.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / chemistry
  • Adenosine A2 Receptor Agonists*
  • Administration, Inhalation
  • Adolescent
  • Adult
  • Animals
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Lung / drug effects
  • Male
  • Middle Aged
  • Models, Chemical
  • Phenethylamines / chemistry
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Purines / chemistry
  • Rats
  • Structure-Activity Relationship
  • Triazoles / chemistry

Substances

  • Adenosine A2 Receptor Agonists
  • GW 328267
  • Phenethylamines
  • Purines
  • Triazoles
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Adenosine