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

Authors

Xiaohua Huang, Merck & Co., Inc.
Cliff C. Cheng, Merck & Co., Inc.
Thierry O. Fischmann, Merck & Co., Inc.
José S. Duca, Merck & Co., Inc.
Matthew Richards, Merck & Co., Inc.
Praveen K. Tadikonda, Merck & Co., Inc.
Panduranga Adulla Reddy, Merck & Co., Inc.
Lianyun Zhao, Merck & Co., Inc.
M. Arshad Siddiqui, Merck & Co., Inc.
David Parry, Merck & Co., Inc.
Nicole Davis, Merck & Co., Inc.
Wolfgang Seghezzi, Merck & Co., Inc.
Derek Wiswell, Merck & Co., Inc.
Gerald W. Shipps, Merck & Co., Inc.

Abstract

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 'U-shaped' topology and key interactions with the protein surface at the ATP site is also reported. © 2013 Elsevier Ltd. All rights reserved.

Publication Title

Journal of the American Chemical Society

Recommended Citation

Huang, X., Cheng, C., Fischmann, T., Duca, J., Richards, M., Tadikonda, P., Reddy, P., Zhao, L., Arshad Siddiqui, M., Parry, D., Davis, N., Seghezzi, W., Wiswell, D., & Shipps, G. (2000). Highly active and selective catalysts for the formation of α-aryl ketones. Journal of the American Chemical Society, 122 (7), 1360-1370. https://doi.org/10.1021/ja993912d