Evaluation of a series of bicyclic CXCR2 antagonists

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.

The SAR of a series of pyrimidine-based fused bicyclic heterocycles at the CXCR2 receptor was investigated, leading to the discovery of a series of potent, bioavailable thiazolo[4,5-d]pyrimidine-2(3H)-one antagonists 30a–f with additional CCR2 activity.Figure optionsDownload as PowerPoint slide