Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10592741 | Bioorganic & Medicinal Chemistry Letters | 2014 | 5 Pages |
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 1, 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 14. 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.
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Authors
David W. Porter, Michelle Bradley, Zarin Brown, Riccardo Canova, Steven Charlton, Brian Cox, Peter Hunt, David Kolarik, Sarah Lewis, Des O'Connor, John Reilly, Carsten Spanka, Lauren Tedaldi, Simon J. Watson, Roland Wermuth, Neil J. Press,