title: SAR of a series of inhaled A(2A) agonists and comparison of inhaled pharmacokinetics in a preclinical model with clinical pharmacokinetic data.
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.
authors.affiliation: Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Kent, CT13 9NJ, United Kingdom. simon.mantell@pfizer.com
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: Don K
authors.initials: DK
authors.lastname: Walker
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: Arnaud
authors.initials: A
authors.lastname: Lemaitre
authors.forename: Karen N
authors.initials: KN
authors.lastname: Wright
authors.forename: Lynsey
authors.initials: L
authors.lastname: Whitlock
authors.forename: Emilio F
authors.initials: EF
authors.lastname: Stuart
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Wright
authors.forename: Fiona
authors.initials: F
authors.lastname: Macintyre
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry; D058908:Adenosine A2 Receptor Agonists; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008168:Lung / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008956:Models, Chemical; D010627:Phenethylamines / Q000737:chemistry; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011687:Purines / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry
chemical_list: D058908:Adenosine A2 Receptor Agonists; C545367:GW 328267; D010627:Phenethylamines; D011687:Purines; D014230:Triazoles; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine