The discovery of potent, orally bioavailable pyrimidine-5-carbonitrile-6-alkyl CXCR2 receptor antagonists

Porter, David W, Bradley, Michelle, Brown, Zarin, Charlton, Steven J, Cox, Brian, Hunt, Peter, Janus, Diana, Lewis, Sarah, Oakley, Paul, O'Connor, Des, Reilly, John, Smith, Nichola and Press, Neil J (2014) The discovery of potent, orally bioavailable pyrimidine-5-carbonitrile-6-alkyl CXCR2 receptor antagonists. Bioorganic & Medicinal Chemistry Letters, 24 (15). pp. 3285-3290. ISSN 0960-894X

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Abstract

A hit-to-lead optimisation programme was carried out on the Novartis archive screening hit, pyrimidine 2-((2,6-dichlorobenzyl)thio)-5-isocyano-6-phenylpyrimidin-4-ol 4, resulting in the discovery of CXCR2 receptor antagonist 2-((2,3-difluorobenzyl)thio)-6-(2-(hydroxymethyl)cyclopropyl)-5-isocyanopyrimidin-4-ol 24. The SAR was investigated by systematic variation of the aromatic group at c-6, the linker between c-2 and the halogenated ring, and the c-5 nitrile moiety.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry
Depositing User: Tom Gittoes
Date Deposited: 12 Jan 2015 11:20
Last Modified: 12 Jan 2015 11:20
URI: http://sro.sussex.ac.uk/id/eprint/52035
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