SAR of a series of inhaled A(2A) agonists and comparison of inhaled pharmacokinetics in a preclinical model with clinical pharmacokinetic data.
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.
Mantell
Simon J
SJ
Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Kent, CT13 9NJ, United Kingdom. simon.mantell@pfizer.com
Stephenson
Peter T
PT
Monaghan
Sandra M
SM
Maw
Graham N
GN
Trevethick
Michael A
MA
Yeadon
Michael
M
Walker
Don K
DK
Selby
Matthew D
MD
Batchelor
David V
DV
Rozze
Stuart
S
Chavaroche
Helene
H
Lemaitre
Arnaud
A
Wright
Karen N
KN
Whitlock
Lynsey
L
Stuart
Emilio F
EF
Wright
Patricia A
PA
Macintyre
Fiona
F
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
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