File(s) not publicly available
The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1- hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting ß2-adrenoceptor agonist
journal contributionposted on 2023-06-08, 19:46 authored by Nicola Arnold, David Beattie, Michelle Bradley, Andrew Brearley, Lyndon Brown, Steven J Charlton, Robin A Fairhurst, David Farr, John Fozard, Joe Fullerton, Martin Gosling, Julia Hatto, Diana Janus, Darryl Jones, Lynne Jordan, Christine Lewis, Janet Maas, Clive McCarthy, Mark Mercer, Helen Oakman, Neil Press, Rachel Profit, Friedrich Schuerch, David Sykes, Roger J Taylor, Alexandre Trifilieff, Andrew Tuffnell
The optimisation of two series of 4-hydroxybenzothiazolone derived ß2-adrenoceptor agonists, bearing a-substituted cyclopentyl and ß-phenethyl amino-substituents, as inhaled long-acting bronchodilators is described. Analogues were selected for synthesis using a lipophilicity based hypothesis to achieve the targeted rapid onset of action in combination with a long duration of action. The profiling of the two series led to identification of the a-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting ß2-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the backup development candidate to indacaterol from the Novartis LABA project. © 2014 Elsevier Ltd. All rights reserved.
JournalBioorganic and Medicinal Chemistry Letters
Department affiliated with
- Chemistry Publications
Full text available