Bioorganic & Medicinal Chemistry Letters 2008-01-15

Evaluation of a series of bicyclic CXCR2 antagonists.

Iain Walters, Caroline Austin, Rupert Austin, Roger Bonnert, Peter Cage, Mark Christie, Mark Ebden, Stuart Gardiner, Caroline Grahames, Steven Hill, Fraser Hunt, Robert Jewell, Shirley Lewis, Iain Martin, David Nicholls, David Robinson

文献索引：Bioorg. Med. Chem. Lett. 18(2) , 798-803, (2008)

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摘要

The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antagonists with markedly improved biological and pharmacokinetic properties, which are suitable pharmacological tools to probe the in vivo effects of CXCR2 antagonism combined with the associated CCR2 activity.