Author/Authors :
Lo، نويسنده , , Ho Yin and Bentzien، نويسنده , , Jِrg and White، نويسنده , , Andre and Man، نويسنده , , Chuk C. and Fleck، نويسنده , , Roman W. and Pullen، نويسنده , , Steven S. and Khine، نويسنده , , Hnin Hnin and King، نويسنده , , Josephine and Woska Jr.، نويسنده , , Joseph R. and Wolak، نويسنده , , John P. and Kashem، نويسنده , , Mohammed A. and Roth، نويسنده , , Gregory P. and Takahashi، نويسنده , , Hide، نويسنده ,
Abstract :
Based on information from molecular modeling, a series of 2-aminobenzimidazoles with pyrrole moieties were designed and synthesized as ITK antagonists. Results showed that a significant improvement of intrinsic and cell-based potency was achieved. X-ray crystallographic analysis of an inhibitor complex with ITK confirmed the prediction from the de novo design that the pyrrole moiety of the inhibitor would form an additional hydrogen bonding interaction with Glu436 in the catalytic domain, and hence improve overall binding affinity of the inhibitor.
