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The discovery of potent, orally bioavailable pyrazolo and triazolopyrimidine CXCR2 receptor antagonists

journal contribution
posted on 2023-06-08, 19:29 authored by 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 Tedaldia, Simon J Watson, Roland Wermuth, Neil J Press
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.

History

Publication status

  • Published

Journal

Bioorganic and Medicinal Chemistry Letters

ISSN

0960-894X

Publisher

Elsevier

Issue

1

Volume

24

Page range

72-76

Department affiliated with

  • Chemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2015-01-12

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