The discovery of indole-derived long acting beta2-adrenoceptor agonists for the treatment of asthma and COPD.
The design and profile of a series of indole containing long acting beta(2)-adrenoceptor agonists is described. Evaluation of these analogues using an in vitro guinea pig trachea tissue model demonstrates that analogues within this series have salmeterol-like duration of action with potential for long duration of action in humans.
Brown
Alan D
AD
Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, UK.
Bunnage
Mark E
ME
Glossop
Paul A
PA
Holbrook
Mark
M
Jones
Rhys D
RD
Lane
Charlotte A L
CA
Lewthwaite
Russell A
RA
Mantell
Simon
S
Perros-Huguet
Christelle
C
Price
David A
DA
Webster
Rob
R
D000318:Adrenergic beta-Agonists / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001682:Biological Availability; D016466:CHO Cells; D018938:Caco-2 Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects*; D000068299:Salmeterol Xinafoate; D013997:Time Factors; D014132:Trachea / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D007211:Indoles; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D000420:Albuterol