Discovery of AZD3199, an inhaled ultralong acting β2 receptor agonist with rapid onset of action

Stocks, Michael and Alcaraz, Lilian and Bailey, Andrew and Bonnert, Roger and Cadogan, Elaine and Christie, Jadeen and Dixon, John and Connolly, Stephen and Cook, Anthony and Fisher, Adrian and Flaherty, Alice and Humphries, Alexander and Ingall, Anthony and Jordan, Stephen and Lawson, Mandy and Mullen, Alex and Nicholls, David and Paine, Stuart and Pairaudeau, Garry and Young, Alan (2014) Discovery of AZD3199, an inhaled ultralong acting β2 receptor agonist with rapid onset of action. ACS Medicinal Chemistry Letters, 5 (4). pp. 416-421. ISSN 1948-5875

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Abstract

A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultra-long acting bronchodilators. Determination of activities at the human β-adrenoreceptors demonstrated a series of highly potent and selective β2 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 β2 receptor agonist with rapid onset of action.

Item Type: Article
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
Schools/Departments: University of Nottingham UK Campus > Faculty of Science > School of Pharmacy
Depositing User: Stocks, Dr Michael
Date Deposited: 17 Apr 2014 14:39
Last Modified: 15 Sep 2016 08:58
URI: http://eprints.nottingham.ac.uk/id/eprint/2950

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