Identification and initial evaluation of 4-N-aryl-[1,4]diazepane ureas as potent CXCR3 antagonists

The identification and evaluation of aryl-[1,4]diazepane ureas as functional antagonists of the chemokine receptor CXCR3 are described. Specific examples exhibit IC50 values of ∼60 nM in a calcium mobilization functional assay, and dose-dependently inhibit CXCR3 functional response to CXCL11 (interferon-inducible T-cell α chemoattractant/I-TAC) as measured by T-cell chemotaxis, with a potency of approximately 100 nM.

Graphical abstractThe synthesis and evaluation of 4-N-aryl-[1,4]diazepane ureas as CXCR3 antagonists are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide