Discovery of a potent and selective aurora kinase inhibitor.

Discovery of a potent and selective aurora kinase inhibitor.

Bioorganic & medicinal chemistry letters (2008-08-06)

Johan D Oslob, Michael J Romanowski, Darin A Allen, Subramanian Baskaran, Minna Bui, Robert A Elling, William M Flanagan, Amy D Fung, Emily J Hanan, Shannon Harris, Stacey A Heumann, Ute Hoch, Jeffrey W Jacobs, Joni Lam, Chris E Lawrence, Robert S McDowell, Michelle A Nannini, Wang Shen, Jeffrey A Silverman, Michelle M Sopko, Bradley T Tangonan, Juli Teague, Josh C Yoburn, Chul H Yu, Min Zhong, Kristin M Zimmerman, Tom O'Brien, Willard Lew

PMID18678489

摘要

This communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models.