4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6

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• 作者：Young Shin Cho ; Maria Borland ; Christopher Brain ; Christine H.-T. Chen ; Hong Cheng ; Rajiv Chopra ; Kristy Chung ; James Groarke ; Guo He ; Ying Hou ; Sunkyu Kim ; Steven Kovats ; Yipin Lu ; Marc O’ ; Reill
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：November 25, 2010
• 年：2010
• 卷：53
• 期：22
• 页码：7938-7957
• 全文大小：1369K
• 年卷期：v.53,no.22(November 25, 2010)
• ISSN：1520-4804

文摘

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.