Porter, David, Bradley, Michelle, Brown, Zarin, Charlton, Steven, Cox, Brian, Hunt, Peter, Janus, Diana, Lewis, Sarah, Oakley, Paul, O'Connor, Des, Reilly, John, Smith, Nichola and Press, Neil (2014) The Discovery of Potent, Orally Bioavailable Pyrimidine-5-carbonitrile-6-alkyl CXCR2 Receptor Antagonists. Biorganic & Medicinal Chemistry Letters.

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
Keywords:	CXCR2
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/20993