The Discovery of Potent, Orally Bioavailable Pyrazolo and Triazolopyrimidine CXCR2 Receptor Antagonists.
Porter, David, Bradley, Michelle, Brown, Zarin, Canova, Riccardo, Charlton, Steven, Cox, Brian, Hunt, Peter, Kolarik, David, Lewis, Sarah, O'Connor, Des, Reilly, John, Spanka, Carsten, Tedaldi, Lauren, Watson, Simon, Wermuth, Roland and Press, Neil (2014) The Discovery of Potent, Orally Bioavailable Pyrazolo and Triazolopyrimidine CXCR2 Receptor Antagonists. Biorganic and Medicinal Chemistry Letters, 24 (1). pp. 72-76.
Abstract
A Hit-to-Lead optimisation programme was carried out on the Novartis archive screening hit, pyrazolopyrimidine 2-methyl-5-((phenylthio)methyl)pyrazolo[1,5-a]pyrimidin-7-ol, resulting in the discovery of CXCR2 receptor antagonist 2-benzyl-5-(((2,3-difluorophenyl)thio)methyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol. The SAR was investigated by systematic variation of the pendant thiol, alkyl and pyrimidinol groups. Replacement of the pyrazolopyrimidine core with a triazolo alternative led to a dual series of antagonists with favourable biological and pharmacokinetic properties.
Item Type: | Article |
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Keywords: | CXCR2 receptor Antagonists |
Date Deposited: | 13 Oct 2015 13:13 |
Last Modified: | 13 Oct 2015 13:13 |
URI: | https://oak.novartis.com/id/eprint/10727 |