2-Aminobenzimidazoles as potent Aurora kinase inhibitors

  • Bioorg Med Chem Lett. 2009 Sep 1;19(17):5158-61. doi: 10.1016/j.bmcl.2009.07.016.
Min Zhong  1 ,  Minna Bui ,  Wang Shen ,  Subramanian Baskaran ,  Darin A Allen ,  Robert A Elling ,  W Michael Flanagan ,  Amy D Fung ,  Emily J Hanan ,  Shannon O Harris ,  Stacey A Heumann ,  Ute Hoch ,  Sheryl N Ivy ,  Jeffrey W Jacobs ,  Stuart Lam ,  Heman Lee ,  Robert S McDowell ,  Johan D Oslob ,  Hans E Purkey ,  Michael J Romanowski ,  Jeffrey A Silverman ,  Bradley T Tangonan ,  Pietro Taverna ,  Wenjin Yang ,  Josh C Yoburn ,  Chul H Yu ,  Kristin M Zimmerman ,  Tom O'Brien ,  Willard Lew
Affiliations
  • 1. Sunesis Pharmaceuticals, Inc., 395 Oyster Point Blvd., South San Francisco, CA 94080, USA. [email protected]
PMID: 19646866 DOI: 10.1016/j.bmcl.2009.07.016
Abstract

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.