Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors

被引：33

作者：

Fucini, Raymond V. ^{[1
]}

Hanan, Emily J. ^{[2
]}

Romanowski, Michael J. ^{[3
]}

Elling, Robert A. ^{[3
]}

Lew, Willard ^{[2
]}

Barr, Kenneth J. ^{[2
]}

Zhu, Jiang ^{[2
]}

Yoburn, Joshua C. ^{[2
]}

Liu, Yang ^{[2
]}

Fahr, Bruce T. ^{[2
]}

Fan, Junfa ^{[2
]}

Lu, Yafan ^{[2
]}

Pham, Phuongly ^{[2
]}

Choong, Ingrid C. ^{[2
]}

VanderPorten, Erica C. ^{[1
]}

Bui, Minna ^{[2
]}

Purkey, Hans E. ^{[2
]}

Evanchik, Marc J. ^{[1
]}

Yang, Wenjin ^{[2
]}

机构：

[1] Sunesis Pharmaceut Inc, Dept Biol, San Francisco, CA 94080 USA

[2] Sunesis Pharmaceut Inc, Dept Chem, San Francisco, CA 94080 USA

[3] Sunesis Pharmaceut Inc, Dept Biol Struct, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 20期

关键词：

2-amino-pyrazolopyridine; Polo-like kinase (Plk); SAR; kinase inhibitor;

D O I：

10.1016/j.bmcl.2008.08.095

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2-amino-pyrazolopyridines was designed and synthesized as Polo-like kinase (Plk) inhibitors based on a low micromolar hit. The SAR was developed to provide compounds exhibiting low nanomolar inhibitory activity of Plk1; the phenotype of treated cells is consistent with Plk1 inhibition. A co-crystal structure of one of these compounds with zPlk1 confirms an ATP-competitive binding mode. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5648 / 5652

页数：5

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