Synthesis and biological evaluation of benzenesulfonamide-substituted 4-(6-alkylpyridin-2-yl)-5-(quinoxalin-6-yl)imidazoles as transforming growth factor-β type 1 receptor kinase inhibitors

被引：18
作者：
Kim, Dae-Kee [1 ]
Jung, Sun Hee [1 ]
Lee, Ho Soon [2 ]
Dewang, Purushottam M. [1 ]
机构：
[1] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea
[2] In2Gen Co Ltd, Seoul 152050, South Korea
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 02期
关键词：
Transforming growth factor-beta (TGF-beta); ALK5; inhibitors; Fibrosis; Cancer; TGF-BETA; ALK5; INHIBITOR; FIBROSIS; MURINE; POTENT;
D O I：
10.1016/j.ejmech.2008.03.024
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of benzenesulfonamide-substituted 4-(6-alkylpyridin-2-yl)-5-(quinoxalin-6-yl)imidazoles (15a-1) have been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 4-[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-ylmethyl]benzenesulfonamide (15b) and 4-[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-ylmethyl]benzene-sulfonamide (15c) showed more than 90% inhibition at 0.5 mu M in a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct, but inhibited p38 alpha MAP kinase activity only 11 and 8% at a concentration of 10 mu M, respectively. (C) 2008 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：568 / 576
页数：9
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