5-Aminomethyl-1H-benzimidazoles as orally active inhibitors of inducible T-cell kinase (Itk)

A series of novel 5-aminomethyl-1H-benzimidazole based inhibitors of Itk were prepared. Structure–activity relationships, selectivity and cell activity are reported for this series. Compound 2, a potent and selective antagonist of Itk, inhibited anti-CD3 antibody induced IL-2 production in vivo in mice.

Graphical abstractThe SAR of this 5-aminomethyl-benzimidazole class of Itk inhibitors is discussed, along with in vivo efficacy in a mouse model.Figure optionsDownload full-size imageDownload as PowerPoint slide