Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade

被引：29

作者：

Berger, D ^{[1
]}

Dutia, M

Powell, D

Wu, BQ

Wissner, A

Boschelli, DH

Floyd, MB

Zhang, N

Torres, N

Levin, J

Du, XM

Wojciechowicz, D

Discafani, C

Kohler, C

Kim, SC

Feldberg, LR

Collins, K

Mallon, R

机构：

[1] Wyeth Res, Chem Sci, Pearl River, NY 10965 USA

[2] Wyeth Res, Discovery Oncol, Pearl River, NY 10965 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 18期

关键词：

D O I：

10.1016/S0960-894X(03)00640-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-6,7-diethoxy-3- quinolinecarbonitrile (3) was identified as a MEK1 kinase inhibitor with exceptional activity against LoVo cells. The structure-activity relationships of the C-4 aniline substituents were explored, and water-solubilizing groups were added at the C-7 position to improve physical properties. Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：3031 / 3034

页数：4

共 16 条

[1]

BROWN DS, 1996, Patent No. 9615118

[2] Agents targeting Ras signaling pathway [J].