Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors

  • Bioorg Med Chem Lett. 2011 Sep 15;21(18):5296-300. doi: 10.1016/j.bmcl.2011.07.027.
Sunny Abraham  1 ,  Michael J Hadd ,  Lan Tran ,  Troy Vickers ,  Janice Sindac ,  Zdravko V Milanov ,  Mark W Holladay ,  Shripad S Bhagwat ,  Helen Hua ,  Julia M Ford Pulido ,  Merryl D Cramer ,  Dana Gitnick ,  Joyce James ,  Alan Dao ,  Barbara Belli ,  Robert C Armstrong ,  Daniel K Treiber ,  Gang Liu
Affiliations
  • 1. Department of Medicinal Chemistry, Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, United States.
PMID: 21802948 DOI: 10.1016/j.bmcl.2011.07.027
Abstract

The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model.