Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802)

被引：147

作者：

Kinoshita, Kazutomo ^{[1
]}

Asoh, Kohsuke ^{[1
]}

Furuichi, Noriyuki ^{[1
]}

Ito, Toshiya ^{[1
]}

Kawada, Hatsuo ^{[1
]}

Hara, Sousuke ^{[1
]}

Ohwada, Jun ^{[1
]}

Miyagi, Takuho ^{[1
]}

Kobayashi, Takamitsu ^{[1
]}

Takanashi, Kenji ^{[1
]}

Tsukaguchi, Toshiyuki ^{[1
]}

Sakamoto, Hiroshi ^{[1
]}

Tsukuda, Takuo ^{[1
]}

Oikawa, Nobuhiro ^{[1
]}

机构：

[1] Chugai Pharmaceut Co Ltd, Div Res, Kamakura, Kanagawa 2478530, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 03期

关键词：

Anaplastic lymphoma kinase; ALK; Kinase inhibitors; CH5424802; NON-HODGKINS-LYMPHOMA; EML4-ALK FUSION GENE; LUNG-CANCER; ALK; IDENTIFICATION; NEUROBLASTOMA; TUMORS;

D O I：

10.1016/j.bmc.2011.12.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is considered an attractive therapeutic target for human cancers, especially non-small cell lung cancer (NSCLC). Our previous study revealed that 8,9-side-chains of 6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b] carbazole scaffold crucially affected kinase selectivity, cellular activity, and metabolic stability. In this work, we optimized the side-chains and identified highly selective, orally active and potent ALK inhibitor CH5424802 (18a) as the clinical candidate. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1271 / 1280

页数：10

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