Itk kinase inhibitors: Initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead

The SAR study and metabolically stabilized benzimidazole class Itk inhibitors is discussed. Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified.