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

被引：87

作者：

Nie, Zhe ^{[1
]}

Perretta, Carin ^{[1
]}

Erickson, Philip ^{[1
]}

Margosiak, Stephen ^{[2
]}

Lu, Jia ^{[2
]}

Averill, April ^{[2
]}

Almassy, Robert ^{[3
]}

Chua, Shaosong ^{[1
]}

机构：

[1] Polaris Pharmaceut Inc, Dept Med Chem, San Diego, CA 92121 USA

[2] Polaris Pharmaceut Inc, Dept Prot Chem, San Diego, CA 92121 USA

[3] Polaris Pharmaceut Inc, Dept Biol Struct, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 02期

关键词：

CK2; kinase; anticancer;

D O I：

10.1016/j.bmcl.2007.11.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 inhibitors with K-i around 1.0 nM and strongly inhibit cancer cell growth with IC50 as low as similar to 100 nM. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：619 / 623

页数：5

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