Discovery and SAR of 2-amino-5-[(thiomethyl)aryl]thiazoles as potent and selective Itk inhibitors

A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure–activity relationships (SARs), selectivity and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 2 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo.

A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure–activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 2 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo.Figure optionsDownload as PowerPoint slide