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

Authors: Abraham S, Hadd MJ, Tran L, Vickers T, Sindac J, Milanov ZV, Holladay MW, Bhagwat SS, Hua H, Ford Pulido JM, Cramer MD, Gitnick D, James J, Dao A, Belli B, Armstrong RC, Treiber DK, Liu G.
Publisher/Year: Bioorg Med Chem Lett. 2011 Sep 15;21(18):5296-300. Epub 2011 Jul 14.
Pub Med ID/Journal ID: PMID:21802948


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. Copyright © 2011 Elsevier Ltd. All rights reserved.