Design and synthesis of orally available MEK inhibitors with potent in vivo antitumor efficacy

被引：16

作者：

Adams, Mark E. ^{[1
]}

Wallace, Michael B. ^{[1
]}

Kanouni, Toufike ^{[1
]}

Scorah, Nicholas ^{[1
]}

O'Connell, Shawn M. ^{[1
]}

Miyake, Hiroshi ^{[1
]}

Shi, Lihong ^{[1
]}

Halkowycz, Petro ^{[1
]}

Zhang, Lilly ^{[1
]}

Dong, Qing ^{[1
]}

机构：

[1] Takeda Calif, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 07期

关键词：

MEK inhibitor; Kinase; Oncology; Dihydroindolone; Dihydroindolizinone; PROTEIN-KINASE KINASE; SIGNALING CASCADE; PATHWAY; CANCER; DERIVATIVES; DISCOVERY;

D O I：

10.1016/j.bmcl.2012.02.026

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：

The structure-based design, synthesis, and biological evaluation of two novel series of potent and selective MEK kinase inhibitors are described herein. The elaboration of a lead pyrrole derivative to a bicyclic dihydroindolone core provided compounds with high potency and good drug-like pharmaceutical properties. Further scaffold modification afforded a series of dihydroindolizinone inhibitors, including an orally available advanced preclinical MEK inhibitor with potent in vivo antitumor efficacy. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2411 / 2414

页数：4

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[2]

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[3]

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[4]

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