title: 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.
authors.affiliation: Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Kent CT13 9NJ, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Mantell
authors.forename: Peter T
authors.initials: PT
authors.lastname: Stephenson
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Monaghan
authors.forename: Graham N
authors.initials: GN
authors.lastname: Maw
authors.forename: Michael A
authors.initials: MA
authors.lastname: Trevethick
authors.forename: Michael
authors.initials: M
authors.lastname: Yeadon
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Keir
authors.forename: Don K
authors.initials: DK
authors.lastname: Walker
authors.forename: Rhys M
authors.initials: RM
authors.lastname: Jones
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Selby
authors.forename: David V
authors.initials: DV
authors.lastname: Batchelor
authors.forename: Stuart
authors.initials: S
authors.lastname: Rozze
authors.forename: Helene
authors.initials: H
authors.lastname: Chavaroche
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Hobson
authors.forename: Peter G
authors.initials: PG
authors.lastname: Dodd
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lemaitre
authors.forename: Karen N
authors.initials: KN
authors.lastname: Wright
authors.forename: Emilio F
authors.initials: EF
authors.lastname: Stuart
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D000280:Administration, Inhalation; D000284:Administration, Oral; D000588:Amines / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D006801:Humans; D008168:Lung / Q000378:metabolism; D010627:Phenethylamines / Q000493:pharmacokinetics / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000588:Amines; D010627:Phenethylamines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine