Highly active and selective catalysts for the formation of α-aryl ketones

Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crystal structure of a complex between compound 39 and the CHK1 protein detailing a \u27U-shaped\u27 topology and key interactions with the protein surface at the ATP site is also reported. © 2013 Elsevier Ltd. All rights reserved