title: Design driven HtL: The discovery and synthesis of new high efficacy β₂-agonists.
abstract: The design and synthesis of a new series of high efficacy β(2)-agonists devoid of the key benzylic alcohol present in previously described highly efficacious β(2)-agonists is reported. A hypothesis for the unprecedented level of efficacy is proposed based on considerations of β(2)-adrenoceptor crystal structure, other biophysical data and modeling studies.
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, UK. mike.stocks@astrazeneca.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stocks
authors.forename: Lilian
authors.initials: L
authors.lastname: Alcaraz
authors.forename: Andrew
authors.initials: A
authors.lastname: Bailey
authors.forename: Roger
authors.initials: R
authors.lastname: Bonnert
authors.forename: Elaine
authors.initials: E
authors.lastname: Cadogan
authors.forename: Jadeen
authors.initials: J
authors.lastname: Christie
authors.forename: Stephen
authors.initials: S
authors.lastname: Connolly
authors.forename: Anthony
authors.initials: A
authors.lastname: Cook
authors.forename: Adrian
authors.initials: A
authors.lastname: Fisher
authors.forename: Alice
authors.initials: A
authors.lastname: Flaherty
authors.forename: Stephen
authors.initials: S
authors.lastname: Hill
authors.forename: Alexander
authors.initials: A
authors.lastname: Humphries
authors.forename: Anthony
authors.initials: A
authors.lastname: Ingall
authors.forename: Stephen
authors.initials: S
authors.lastname: Jordan
authors.forename: Mandy
authors.initials: M
authors.lastname: Lawson
authors.forename: Alex
authors.initials: A
authors.lastname: Mullen
authors.forename: David
authors.initials: D
authors.lastname: Nicholls
authors.forename: Stuart
authors.initials: S
authors.lastname: Paine
authors.forename: Garry
authors.initials: G
authors.lastname: Pairaudeau
authors.forename: Stephen
authors.initials: S
authors.lastname: St-Gallay
authors.forename: Alan
authors.initials: A
authors.lastname: Young
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists