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The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting beta2-adrenoceptor agonist

Arnold, Nicola and Beattie, David and Bradley, Michelle and Brearley, Andrew and Brown, Lyndon and Charlton, Steven and Farr, David Colin and Fozard, John R. and Fullerton, Joe and Gosling, Martin and Hatto, Julia and Janus, Diana and Jones, Darryl and Jordan, Lynne and Lewis, Christine and Maas, Janet and Mercer, Mark and Oakman, Helen and Press, Neil and Profit, Rachael and Schuerch, Friedrich and Sykes, David and Taylor, Roger and Trifilieff, Alexandre and Tuffnell, Andrew and Mccarthy, Clive (2014) The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting beta2-adrenoceptor agonist. Bioorganic and Medicinal Chemistry Letters, 24. pp. 4341-4347.

Abstract

The optimisation of two series of 8-hydroxyquinolinone derived beta2-adrenoceptor agonists, bearing beta-substituted cyclopentyl and beta-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 alpha-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inaled once-daily long-acting beta2-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the back up development candidate to indacaterol from the Novartis LABA project.

Item Type: Article
Keywords: Asthma, COPD, beta-2 adrenoceptor agonist
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21019

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