کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1363555 | 981515 | 2010 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Discovery of olodaterol, a novel inhaled β2-adrenoceptor agonist with a 24 h bronchodilatory efficacy Discovery of olodaterol, a novel inhaled β2-adrenoceptor agonist with a 24 h bronchodilatory efficacy](/preview/png/1363555.png)
Compound 4p was identified from a series of 6-hydroxy-4H-benzo[1,4]oxazin-3-ones as potent agonist of the human β2-adrenoceptor with a high β1/β2-selectivity. A complete reversal of acetylcholine-induced bronchoconstriction which lasted over the whole study period of 5 h 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.
The discovery of the β2-adrenoceptor agonist (R)-4p designated olodaterol is described. The preclinical profile of the compound suggests a bronchoprotective effect over 24 h in humans.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 4, 15 February 2010, Pages 1410–1414