A Physical Properties Based Approach for the Exploration of a 4-Hydroxybenzothiazolone Series of Beta2-Adrenoceptor Agonists as Inhaled Long-Acting Bronchodilators
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Beattie, David, Bradley, Michelle, Brearley, Andrew, Charlton, Steven, Cuenoud, Bernard, Fairhurst, Robin, Gedeck, Peter, Gosling, Martin, Janus, Diana, Jones, Darryl, Lewis, Christine, Mccarthy, Clive, Oakman, Helen, Stringer, Rowan, Taylor, Roger and Tuffnell, Andrew (2010) A Physical Properties Based Approach for the Exploration of a 4-Hydroxybenzothiazolone Series of Beta2-Adrenoceptor Agonists as Inhaled Long-Acting Bronchodilators. Bioorganic and Medicinal Chemistry Letters, 20 (17). pp. 5302-5307.
Abstract
The chiral synthesis of a 4-hydroxybenzothiazolone based series of beta2-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 beta-phenethyl, alpha-substituted cyclopentyl and monoterpene N-substituents to be of interest for further evaluation, as exemplified by structures 19, 29 and 33 respectively.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
| Keywords: | Bronchodilator; b2-Adrenoceptor agonist; 4-Hydroxybenzothiazolone |
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| Date Deposited: | 13 Oct 2015 13:16 |
| Last Modified: | 13 Oct 2015 13:16 |
| URI: | https://oak.novartis.com/id/eprint/2601 |