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An Investigation into the Structure Activity Relationships Associated with the Systematic Modification of the beta2-Adrenoceptor Agonist Indacaterol

Beattie, David and Beer, David and Bradley, Michelle and Bruce, Ian and Charlton, Steven and Cuenoud, Bernard and Fairhurst, Robin and Farr, David Colin and Fozard, John R. and Janus, Diana and Rosethorne, Elizabeth and Sandham, David and Sykes, David and Trifilieff, Alexandre and Turner, Katharine and Wissler, Elke (2012) An Investigation into the Structure Activity Relationships Associated with the Systematic Modification of the beta2-Adrenoceptor Agonist Indacaterol. Bioorganic & medicinal chemistry letters, 22 (19). pp. 6280-6285. ISSN 0960-894X

Abstract

The synthesis of a series of indacaterol analogues in which each of the three structural regions of indacaterol are modified in a systematic manner is described. Evaluation of the affinity of these analogues for the 2-adrenoceptor identified the 3,4-dihydroquinolinone and 5-n-butylindanyl analogues to demonstrate the most similar profiles to indacterol. An -methyl aminoindan analogue was discovered to be 25-fold more potent than indacaterol, and functional studies revealed an atypical 2-adrenoceptor activation profile for this compound consistent with that of a slowly dissociating ‘super agonist’.

Item Type: Article
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Additional Information: A paid open access option is available for this journal.
Keywords: Beta-2 adrenoceptor agonists; COPD; indacaterol; binding kinetics; bronchodilator
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/6265

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