Author/Authors :
Roger J. Snow، نويسنده , , Asitha Abeywardane، نويسنده , , Scot Campbell، نويسنده , , John Lord، نويسنده , , Mohammed A. Kashem، نويسنده , , Hnin Hnin Khine، نويسنده , , Josephine King، نويسنده , , Jennifer A. Kowalski، نويسنده , , Steven S. Pullen، نويسنده , , Teresa Roma، نويسنده , , Gregory P. Roth، نويسنده , , Christopher R. Sarko، نويسنده , , Noel S. Wilson، نويسنده , , Michael P. Winters، نويسنده , , John P. Wolak، نويسنده , , Charles L. Cywin، نويسنده ,
Abstract :
Benzimidazole 1 was identified as a selective inhibitor of ITK by high throughput screening. Hit-to-lead studies defined the SAR at all three substituents. Reversing the amide linkage at C6 led to 16, with a fivefold improvement of potency. This enhancement is rationalized by the conformational preference of the substituent. A model for the binding of the benzimidazoles to the ATP-binding site of ITK is proposed.
Keywords :
ITK , kinase inhibitor , Benzimidazole , Inducible T cell kinase , kinase
