Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors
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- 作者：Kirk L. Stevens ; Michael J. Reno ; Jennifer B. Alberti ; Daniel J. Price ; Laurie S. Kane-Carson ; Victoria B. Knick ; Lisa M. Shewchuk ; Anne M. Hassell ; James M. Veal ; Stephen T. Davis ; Robert J. Griffin
- 关键词：Cyclin-dependant kinase inhibitor ; CDK2 ; CDK4 ; VEGFR-2 ; GSK3β ; Pyrazolo[1 ; 5-b] pyridazine ; Cancer
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：1 November 2008
- 年：2008
- 卷：18
- 期：21
- 页码：5758-5762
- 全文大小：241 K
文摘
A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modification of the hinge-binding amine or the C(2)- and C(6)-substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3β.