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

被引：144
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
收藏
页码：1271 / 1280
页数：10
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