Design driven HtL: The discovery and synthesis of new high efficacy β 2 -agonists

The design and synthesis of a new series of high efficacy β2-agonists devoid of the key benzylic alcohol present in previously described highly efficacious β2-agonists is reported. A hypothesis for the unprecedented level of efficacy is proposed based on considerations of β2-adrenoceptor crystal structure, other biophysical data and modeling studies.