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
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