Identification of novel, potent and selective inhibitors of Polo-like kinase 1

被引：37

作者：

Chen, Shaoqing ^{[1
]}

Bartkovitz, David ^{[1
]}

Cai, Jianping ^{[1
]}

Chen, Yi ^{[1
]}

Chen, Zhi ^{[1
]}

Chu, Xin-Jie ^{[1
]}

Le, Kang ^{[1
]}

Le, Nam T. ^{[1
]}

Luk, Kin-Chun ^{[1
]}

Mischke, Steve ^{[1
]}

Naderi-Oboodi, Goli ^{[1
]}

Boylan, John F. ^{[2
]}

Nevins, Tom ^{[2
]}

Qing, Weiguo ^{[2
]}

Chen, Yingsi ^{[3
]}

Wovkulich, Peter M. ^{[1
]}

机构：

[1] Hoffmann La Roche Inc, Discovery Chem, Pharma Res & Early Dev, Small Mol Res, Nutley, NJ 07110 USA

[2] Hoffmann La Roche Inc, Discovery Oncol, Pharma Res & Early Dev, Small Mol Res, Nutley, NJ 07110 USA

[3] Hoffmann La Roche Inc, Discovery Technol, Pharma Res & Early Dev, Small Mol Res, Nutley, NJ 07110 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 02期

关键词：

Polo-like kinase 1 (PLK1); Pyrimidodiazepines; Kinase inhibitor; Antitumor agent; CANCER-THERAPY; PHASE-I; BI; 2536; BENZOTRIAZOLE; MALIGNANCIES; ONCOLOGY; SCREEN; TARGET; DOMAIN; CELLS;

D O I：

10.1016/j.bmcl.2011.11.052

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A series of pyrimidodiazepines was identified as potent Polo-like kinase 1 (PLK1) inhibitors. The synthesis and SAR are discussed. The lead compound 7 (RO3280) has potent inhibitory activity against PLK1, good selectivity against other kinases, and excellent in vitro cellular potency. It showed strong antitumor activity in xenograft mouse models. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1247 / 1250

页数：4

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