The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1- hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist

Arnold, Nicola, Beattie, David, Bradley, Michelle, Brearley, Andrew, Brown, Lyndon, Charlton, Steven J, Fairhurst, Robin A, Farr, David, Fozard, John, Fullerton, Joe, Gosling, Martin, Hatto, Julia, Janus, Diana, Jones, Darryl, Jordan, Lynne, Lewis, Christine, Maas, Janet, McCarthy, Clive, Mercer, Mark, Oakman, Helen, Press, Neil, Profit, Rachel, Schuerch, Friedrich, Sykes, David, Taylor, Roger J, Trifilieff, Alexandre and Tuffnell, Andrew (2014) The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1- hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist. Bioorganic and Medicinal Chemistry Letters, 24 (17). pp. 4341-4347. ISSN 0960-894X

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Abstract

The optimisation of two series of 4-hydroxybenzothiazolone derived β2-adrenoceptor agonists, bearing α-substituted cyclopentyl and β-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 α-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting β2-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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry
Depositing User: Tom Gittoes
Date Deposited: 27 Jan 2015 09:50
Last Modified: 27 Jan 2015 09:50
URI: http://sro.sussex.ac.uk/id/eprint/52451
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