A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of β2-adrenoceptor agonists as inhaled long-acting bronchodilators

Beattie, David, Bradley, Michelle, Brearley, Andrew, Charlton, Steven J, Cuenoud, Bernard M, Fairhurst, Robin A, Gedeck, Peter, Gosling, Martin, Janus, Diana, Jones, Darryl, Lewis, Christine, McCarthy, Clive, Oakman, Helen, Stringer, Rowan, Taylor, Roger J and Tuffnell, Andrew (2010) A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of β2-adrenoceptor agonists as inhaled long-acting bronchodilators. Bioorganic and Medicinal Chemistry Letters, 20 (17). pp. 5302-5307. ISSN 0960-894X

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Abstract

The chiral synthesis of a 4-hydroxybenzothiazolone based series of β2-adrenoceptor agonists is described. Using this methodology a library of N-substituted analogues were prepared for the rapid identification of leads with the potential to be fast onset and long-acting inhaled bronchodilators with improved therapeutic margins. The design of the library to achieve the targeted profile was based upon lipophilicity and metabolism based hypotheses. This approach identified β-phenethyl, α-substituted cyclopentyl and monoterpene N-substituents to be of particular interest for further evaluation, as exemplified by structures 19, 29 and 33, respectively. © 2010 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 09:33
Last Modified: 27 Jan 2015 09:33
URI: http://sro.sussex.ac.uk/id/eprint/52456
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