2-Aminobenzimidazoles as potent ITK antagonists: de novo design of a pyrrole system targeting additional hydrogen bonding interaction

…, HH Khine, J King, JR Woska, JP Wolak, MA Kashem…

Index: Lo, Ho Yin; Bentzien, Joerg; White, Andre; Man, Chuk C.; Fleck, Roman W.; Pullen, Steven S.; Khine, Hnin Hnin; King, Josephine; Woska Jr., Joseph R.; Wolak, John P.; Kashem, Mohammed A.; Roth, Gregory P.; Takahashi, Hidenori Tetrahedron Letters, 2008 , vol. 49, # 51 p. 7337 - 7340

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Citation Number: 17

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 ...