Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors

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• 作者：Dezhi Yang ; Peng Wang ; Jianzhen Liu ; Hualu Xing ; Yang Liu ; Wencheng Xie ; Guisen Zhao
• 关键词：AKT inhibitors ; GSK3尾 ; Inhibition rate ; Tetra-substituted indoles
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：1 January, 2014
• 年：2014
• 卷：22
• 期：1
• 页码：366-373
• 全文大小：2331 K

文摘

Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1, with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of 10 nM. In addition, compounds 6a and 6o also potently inhibited the phosphorylation of the downstream GSK3 protein and displayed slightly better anti-proliferative activities in a prostate cancer cell line.