Discovery, SAR and X-ray structure of 1H-benzimidazole-5-carboxylic acid cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk)

Autor:	Michael P. Winters, Renee L. DesJarlais, Mark Bobko, John P. Wolak, Ho Yin Lo, Steven S. Pullen, Deborah D. Jeanfavre, Hnin Hnin Khine, Rosemarie H. Sallati, Ernest L. Raymond, Mohammed A. Kashem, Lei Qiao, Gregory P. Roth, Declan Ryan, Joseph R. Woska, Kevin J. Moriarty, Darius Robinson, Hidenori Takahashi, B. Tomczuk, Wilson Matthew Allan, Ronald L. Magolda, Peter Allen Nemoto, Andre White, Brian Nicholas Cook
Rok vydání:	2008
Předmět:	Benzimidazole Molecular model medicine.drug_class Stereochemistry Chemistry Pharmaceutical Carboxylic acid Clinical Biochemistry Carboxylic Acids Molecular Conformation Pharmaceutical Science Carboxamide Crystallography X-Ray Biochemistry Chemical synthesis Inhibitory Concentration 50 Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Enzyme Inhibitors skin and connective tissue diseases Molecular Biology chemistry.chemical_classification biology Bicyclic molecule Kinase fungi Organic Chemistry Protein-Tyrosine Kinases Amides body regions Models Chemical chemistry Enzyme inhibitor Drug Design Microsomes Liver biology.protein Molecular Medicine Benzimidazoles
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 18:5545-5549
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2008.09.015
Popis:	A series of novel potent benzimidazole based inhibitors of interleukin-2 T-cell kinase (Itk) were prepared. In this report, we discuss the structure-activity relationship (SAR), selectivity, and cell-based activity for the series. We also discuss the SAR associated with an X-ray structure of one of the small-molecule inhibitors bound to ITK.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77216c0a135ce0c04945949b146cd09c https://doi.org/10.1016/j.bmcl.2008.09.015 Zobrazit plný text záznamu Full Text from ScienceDirect