Discovery of AZD3199, An Inhaled Ultralong Acting ?2 Receptor Agonist with Rapid Onset of Action

Stocks, Michael; Alcaraz, Lilian; Bailey, Andrew; Bonnert, Roger; Cadogan, Elaine; Christie, Jadeen; Dixon, John; Connolly, Stephen; Cook, Anthony; Fisher, Adrian; Flaherty, Alice; Humphries, Alexander; Ingall, Anthony; Jordan, Stephen; Lawson, Mandy; Mullen, Alex; Nicholls, David; Paine, Stuart; Pairaudeau, Garry; Young, Alan

doi:10.1021/ml4005232

Discovery of AZD3199, An Inhaled Ultralong Acting ?2 Receptor Agonist with Rapid Onset of Action

Stocks, Michael; Alcaraz, Lilian; Bailey, Andrew; Bonnert, Roger; Cadogan, Elaine; Christie, Jadeen; Dixon, John; Connolly, Stephen; Cook, Anthony; Fisher, Adrian; Flaherty, Alice; Humphries, Alexander; Ingall, Anthony; Jordan, Stephen; Lawson, Mandy; Mullen, Alex; Nicholls, David; Paine, Stuart; Pairaudeau, Garry; Young, Alan

Authors

MICHAEL STOCKS MICHAEL.STOCKS@NOTTINGHAM.AC.UK
Professor of Medicinal Chemistry and Drug Discovery

Lilian Alcaraz

Andrew Bailey

Roger Bonnert

Elaine Cadogan

Jadeen Christie

John Dixon

Stephen Connolly

Anthony Cook

Adrian Fisher

Alice Flaherty

Alexander Humphries

Anthony Ingall

Stephen Jordan

Mandy Lawson

Alex Mullen

David Nicholls

STUART PAINE Stuart.Paine@nottingham.ac.uk
Associate Professor

Garry Pairaudeau

Alan Young

Abstract

A series of dibasic des-hydroxy ?2 receptor agonists has been prepared and evaluated for potential as inhaled ultra-long acting bronchodilators. Determination of activities at the human ?-adrenoreceptors demonstrated a series of highly potent and selective ?2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by; onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i. t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultra-long acting inhaled ?2 receptor agonist with rapid onset of action.

Citation

Stocks, M., Alcaraz, L., Bailey, A., Bonnert, R., Cadogan, E., Christie, J., …Young, A. (2014). Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. ACS Medicinal Chemistry Letters, 5(4), 416-421. https://doi.org/10.1021/ml4005232

Journal Article Type	Article
Acceptance Date	Feb 8, 2014
Online Publication Date	Feb 11, 2014
Publication Date	Apr 10, 2014
Deposit Date	Apr 17, 2014
Publicly Available Date	Apr 17, 2014
Journal	ACS Medicinal Chemistry Letters
Print ISSN	1948-5875
Electronic ISSN	1948-5875
Publisher	American Chemical Society
Peer Reviewed	Peer Reviewed
Volume	5
Issue	4
Pages	416-421
DOI	https://doi.org/10.1021/ml4005232
Public URL	https://nottingham-repository.worktribe.com/output/723363
Publisher URL	https://pubs.acs.org/doi/10.1021/ml4005232
Additional Information	This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in ACS Medicinal Chemistry Letters copyright © American Chemical Society after peer review. To access the final edited and published work see: http://pubs.acs.org/doi/ipdf/10.1021/ml4005232