Structure-based design and synthesis of novel macrocyclic pyrazolo[1,5-a][1,3,5]triazine compounds as potent inhibitors of protein kinase CK2 and their anticancer activities

Z. Nie, C. Perretta, P. Ericksin, S. Margosiak, J. Lu, A. Averill, R. Almassy and S. Chu
Bioorganic & Medicinal Chemistry Letters (2008), Vol. 18 pages 619-623

A series of macrocyclic derivatives has been designed and synthesized based on the X-ray co-crystal structures of pyrazolo[1,5-a] [1,3,5]triazines with corn CK2 (cCK2) protein. Bioassays demonstrated that these macrocyclic pyrazolo[1,5-a][1,3,5]triazine compounds are potent CK2 inihibitors with K9i) around 1.0 nM and strongly inhibit cancer cell growth IC(50) as low as approximately 100 nM.