Structure-based design of imidazo[1,2-a] pyrazine derivatives as selective inhibitors of Aurora-A kinase in cells

Co-crystallisation of the imidazo[ 1,2-a] pyrazine derivative 15 (3-chloro-N-(4-morpholinophenyl)-6-( pyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine) with Aurora-A provided an insight into the interactions of this class of compound with Aurora kinases. This led to the design and synthesis of potent Aurora-A inhibitors demonstrating up to 70-fold selectivity in cell-based Aurora kinase pharmacodynamic biomarker assays. (c) 2010 Elsevier Ltd. All rights reserved.