Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1410-4. doi: 10.1016/j.bmcl.2009.12.087. Epub 2010 Jan 4.


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.

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists*
  • Animals
  • Benzoxazines / chemical synthesis
  • Benzoxazines / chemistry*
  • Benzoxazines / pharmacology*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / chemistry*
  • Bronchodilator Agents / pharmacology
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Dogs
  • Guinea Pigs
  • Humans
  • Male
  • Molecular Structure
  • Recombinant Proteins / genetics
  • Stereoisomerism
  • Treatment Outcome


  • Adrenergic beta-2 Receptor Agonists
  • Benzoxazines
  • Bronchodilator Agents
  • Recombinant Proteins
  • olodaterol