Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
Bioorg Med Chem Lett
; 20(4): 1410-4, 2010 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-20096576
ABSTRACT
Compound 4p was identified from a series of 6-hydroxy-4H-benzo[1,4]oxazin-3-ones as potent agonist of the human beta2-adrenoceptor with a high beta1/beta2-selectivity. A complete reversal of acetylcholine-induced bronchoconstriction which lasted over the whole study period of 5h was demonstrated for 4p in a guinea pig in vivo model without any signs of cardiovascular effects up to 10-fold above the first dose reaching 100% bronchoprotection. The enantiomerically pure (R)-form of 4p exerted a bronchodilatory efficacy over 24 h in dogs and guinea pigs in the absence of systemic pharmacodynamic effects. Formoterol which was tested as comparator in the same in vivo models of acetylcholine-induced bronchoconstriction did not retain efficacy after 24 h. In summary, the preclinical profile of compound (R)-4p (olodaterol, also known as BI 1744 CL) suggests a potential for once-daily dosing in man accompanied with an improved safety profile.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Broncodilatadores
/
Benzoxazinas
/
Agonistas de Receptores Adrenérgicos beta 2
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Alemanha