Palladium-catalyzed direct addition of arylboronic acids to 2-aminobenzonitrile derivatives: synthesis, biological evaluation and in silico analysis of 2-aminobenzophenones, 7-benzoyl-2-oxoindolines, and 7-benzoylindoles
Palladium-catalyzed direct addition of arylboronic acids to 2-aminobenzonitrile derivatives: synthesis, biological evaluation and in silico analysis of 2-aminobenzophenones, 7-benzoyl-2-oxoindolines, and 7-benzoylindoles
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钯催化芳基硼酸直接加成至 2-氨基苯甲腈衍生物：2-氨基二苯甲酮、7-苯甲酰基-2-氧代吲哚啉和 7-苯甲酰基吲哚的合成、生物学评价和计算机分析
DOI：
10.1039/c4ob00978a
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发表时间：
2014-01-01
影响因子：
3.2
通讯作者：
Su, Weike
中科院分区：
文献类型：
--
作者：
Chen, Jiuxi;Ye, Leping;Su, Weike
研究了钯催化芳基硼酸与未保护的2-氨基苯甲腈的直接加成反应，得到了一系列2-氨基二苯甲酮，产率中等至优异。该转化具有广泛的范围和高的官能团耐受性。此外，2-氧代吲哚啉-7-甲腈和吲哚-7-甲腈可分别用于构建7-苯甲酰基-2-氧代吲哚啉和7-苯甲酰基吲哚。在所检测的化合物中，化合物4 e对H446和HGC-27具有最强的体外抗癌活性，其IC 50值分别为0.02 μ mol L-1和0.09 μ mol L-1，而化合物4a对SGC-7901显示出最强的抗癌活性，其IC 50值为0.01 μ mol L-1。此外，我们还进行了计算机分子对接计算，以研究所检查的化合物与其微管蛋白靶标之间的相互作用模式和结合亲和力。
A palladium-catalyzed direct addition of arylboronic acids to unprotected 2-aminobenzonitriles has been developed, leading to a wide range of 2-aminobenzophenones with moderate to excellent yields. The transformation has broad scope and high functional group tolerance. Moreover, 2-oxoindoline-7-carbonitrile and indole-7-carbonitrile were applicable to this process for the construction of 7-benzoyl-2-oxoindolines and 7-benzoylindoles, respectively. Among the compounds examined, compound 4e possessed the most potent anticancer activity against H446 and HGC-27 in vitro, with IC50 values of 0.02 mu mol L-1 and 0.09 mu mol L-1, respectively, while compound 4a showed the best potent anticancer activity against SGC-7901 with an IC50 value of 0.01 mu mol L-1. Furthermore, we also performed in silico molecular docking calculations to investigate the interaction mode and binding affinity between the examined compounds and their tubulin target.