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

Autor:	Andre White, Joseph R. Woska, Ho Yin Lo, Josephine King, John P. Wolak, Mohammed A. Kashem, Jörg Bentzien, Hnin Hnin Khine, Roman Wolfgang Fleck, Steven S. Pullen, Chuk Chui Man, Gregory P. Roth, Hidenori Takahashi
Rok vydání:	2008
Předmět:	chemistry.chemical_compound Molecular model Stereochemistry Hydrogen bond Chemistry Inhibitor complex Organic Chemistry Drug Discovery Moiety Biochemistry Combinatorial chemistry Catalysis Pyrrole
Zdroj:	Tetrahedron Letters. 49:7337-7340
ISSN:	0040-4039
DOI:	10.1016/j.tetlet.2008.10.057
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::0bf5c55c7c49b4297d1b889eb3578745 https://doi.org/10.1016/j.tetlet.2008.10.057 Zobrazit plný text záznamu Full Text from ScienceDirect