Potent and selective mitogen-activated protein kinase kinase (MEK) 1,2 inhibitors.: 1.: 4-(4-bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones

被引：42

作者：

Wallace, EM ^{[1
]}

Lyssikatos, J ^{[1
]}

Blake, JF ^{[1
]}

Seo, J ^{[1
]}

Yang, HW ^{[1
]}

Yeh, TC ^{[1
]}

Perrier, M ^{[1
]}

Jarski, H ^{[1
]}

Marsh, V ^{[1
]}

Poch, G ^{[1
]}

Livingston, MG ^{[1
]}

Otten, J ^{[1
]}

Hingorani, G ^{[1
]}

Woessner, R ^{[1
]}

Lee, P ^{[1
]}

Winkler, J ^{[1
]}

Koch, K ^{[1
]}

机构：

[1] Array BioPharma, Boulder, CO 80301 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 02期

关键词：

D O I：

10.1021/jm050834y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The role of MEK 1,2 in cancer tumorgenesis has been clearly demonstrated preclinically, and two selective inhibitors are currently undergoing clinical evaluation to determine their role in the human disease. We have discovered 4-(4-bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones as a new class of ATP noncompetitive MEK inhibitors. These inhibitors exhibit excellent cellular potency and good pharmacokinetic properties and have demonstrated the ability to inhibit ERK phosphorylation in HT-29 tumors from mouse xenograft studies.

引用

页码：441 / 444

页数：4

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