Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles as inhibitors of transforming growth factor-¦Â type I receptor (ALK5)

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• 作者：Changbin Guo ; Chong Zhang ; Xingzhou Li ; Wei Li ; Zhongliang Xu ; Liangliang Bao ; Yue Ding ; Lili Wang ; Song Li
• 关键词：Transforming growth factor ¦Â ; ALK5 ; Kinase inhibitor ; Imidazole derivatives
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 November, 2013
• 年：2013
• 卷：23
• 期：21
• 页码：5850-5854
• 全文大小：1335 K

文摘

A series of 2-(6-methylpyridin-2-yl)-1H-imidazoles were synthesized and evaluated for ALK5 inhibitory activity in cell-based luciferase reporter assays. The compound 4-(((1-(benzo[d][1,3]dioxol-5-yl)-2-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)methyl)amino)benzenesulfonamide (27a) exhibited slightly higher inhibition (IC₅₀ = 0.24 ¦ÌM) than SB431542 (IC₅₀ = 0.35 ¦ÌM), a well known potent ALK5 inhibitor. The binding mode of 27a generated by flexible docking study shows that it fits well into the site cavity of ALK5 by forming several tight interactions.