4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6
Journal of Medicinal Chemistry2010Vol. 53(22), pp. 7938–7957
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Young Shin Cho, Maria Borland, Christopher T. Brain, Christine H.-T. Chen, Hong Cheng, Rajiv Chopra, Kristy Chung, James M. Groarke, Guo‐Wei He, Ying Hou, Sunkyu Kim, Steven Kovats, Yipin Lu, Marc O’Reilly, Junqing Shen, Troy Smith, G M Trakshel, Markus Vögtle, Mei Ying Xu, Ming Xu, Moo Je Sung
Abstract
Identification and structure-guided optimization of a series of 4-(pyrazol-4-yl)-pyrimidines as selective CDK4/6 inhibitors is reported herein. Several potency and selectivity determinants were established based on the X-ray crystallographic analysis of representative compounds bound to monomeric CDK6. Significant selectivity for CDK4/6 over CDK1 and CDK2 was demonstrated with several compounds in both enzymatic and cellular assays.
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