The discovery of adamantyl-derived, inhaled, long acting beta(2)-adrenoreceptor agonists.
Brown AD, Bunnage ME, Glossop PA, James K, Jones R, Lane CA, Lewthwaite RA, Mantell S, Perros-Huguet C, Price DA, Trevethick M, Webster R.
The design and profile of a series of adamantyl-containing long acting beta(2)-adrenoreceptor agonists are described. An optimal pharmacokinetic profile of low oral bioavailability was combined with a strong pharmacology profile when assessed using a guinea pig trachea tissue model. A focus was then placed on developing a robust synthetic route to ensure rapid delivery of material for clinical trials.