Phthalazinone Pyrazoles as Potent, Selective, and Orally Bioavailable Inhibitors of Aurora-A Kinase

被引：75

作者：

Prime, Michael E. ^{[1
]}

Courtney, Stephen M. ^{[1
]}

Brookfield, Frederick A. ^{[1
]}

Marston, Richard W. ^{[1
]}

Walker, Victoria ^{[1
]}

Warne, Justin ^{[1
]}

Boyd, Andrew E.

Kairies, Norman A. ^{[3
]}

von der Saal, Wolfgang ^{[2
]}

Limberg, Anja ^{[2
]}

Georges, Guy ^{[2
]}

Engh, Richard A. ^{[3
]}

Goller, Bernhard ^{[2
]}

Rueger, Petra ^{[2
]}

Rueth, Matthias ^{[2
]}

机构：

[1] Evotec UK Ltd, Abingdon OX14 4SA, Oxon, England

[2] Roche Diagnost GmbH, Pharma Res Penzberg, D-82372 Penzberg, Germany

[3] Max Planck Inst Biochem, D-82152 Planegg Martinsried, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 01期

关键词：

AURORA/IP11-RELATED PROTEIN-KINASE; SMALL-MOLECULE INHIBITOR; IN-VIVO; ANTICANCER AGENTS; B KINASE; SPINDLE; CELLS; CYTOKINESIS; CHECKPOINT; DISCOVERY;

D O I：

10.1021/jm101346r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature We report a novel class of Aurora kinase inhibitors based upon a phthalazinone pyrazole scoff old The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically > 1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680

引用

页码：312 / 319

页数：8

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