4,5-Dihydro-1H-pyrazolo[4,3-h]quinazolines as potent and selective Polo-like kinase 1 (PLK1) inhibitors

被引：28

作者：

Beria, Italo ^{[1
]}

Valsasina, Barbara ^{[1
]}

Brasca, Maria Gabriella ^{[1
]}

Ceccarelli, Walter ^{[1
]}

Colombo, Maristella ^{[1
]}

Cribioli, Sabrina ^{[1
]}

Fachin, Gabriele ^{[1
]}

Ferguson, Ronald D. ^{[1
,2
]}

Fiorentini, Francesco ^{[2
]}

Gianellini, Laura M. ^{[1
]}

Giorgini, Maria L. ^{[1
]}

Moll, Jurgen K. ^{[1
]}

Posteri, Helena ^{[1
]}

Pezzetta, Daniele ^{[2
]}

Roletto, Fulvia ^{[1
]}

Sola, Francesco ^{[1
]}

Tesei, Dania ^{[1
]}

Caruso, Michele ^{[1
]}

机构：

[1] Nerviano Med Sci Srl, Business Unit Oncol, I-20014 Milan, Italy

[2] Accelera, I-20014 Milan, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 22期

关键词：

PLK1; Polo-like kinase; Kinase inhibitor; In vivo activity; CHECKPOINT; CANCER;

D O I：

10.1016/j.bmcl.2010.09.060

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 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives was optimized as Polo-like kinase 1 inhibitors. Extensive SAR afforded a highly potent and selective PLK1 compound. The compound showed good antiproliferative activity when tested in a panel of tumor cell lines with PLK1 related mechanism of action and with good in vivo antitumor efficacy in two xenograft models after iv administration. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6489 / 6494

页数：6

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