2-Aminobenzimidazoles as potent Aurora kinase inhibitors

Autor:	Willard Lew, Ute Hoch, Jeffrey A. Silverman, Stacey A. Heumann, Sheryl N. Ivy, Stuart Lam, Minna Bui, Hanan Emily, Thomas O'Brien, W. Michael Flanagan, Robert A. Elling, Bradley T. Tangonan, Hans E. Purkey, Heman Lee, Min Zhong, Subramanian Baskaran, Kristin M. Zimmerman, Pietro Taverna, Robert S. McDowell, Amy D. Fung, Wang Shen, Shannon O. Harris, Michael J. Romanowski, Wenjin Yang, Jeffrey W. Jacobs, Joshua C. Yoburn, Darin Allen, Chul Yu, Johan D. Oslob
Rok vydání:	2009
Předmět:	animal structures Clinical Biochemistry Aurora inhibitor Pharmaceutical Science Antineoplastic Agents Protein Serine-Threonine Kinases Biochemistry Mice Structure-Activity Relationship chemistry.chemical_compound Aurora kinase Aurora Kinases In vivo Cell Line Tumor Drug Discovery Animals Humans Structure–activity relationship Protein Kinase Inhibitors Molecular Biology chemistry.chemical_classification biology Organic Chemistry Enzyme chemistry Enzyme inhibitor biology.protein Molecular Medicine Benzimidazoles Bioisostere Signal transduction
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:5158-5161
ISSN:	0960-894X
Popis:	This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e3f97920374b8e6e5f11cd9c42ab0bc https://doi.org/10.1016/j.bmcl.2009.07.016 Zobrazit plný text záznamu Full Text from ScienceDirect