Discovery of 1-arylpyrrolidone derivatives as potent p53-MDM2 inhibitors based on molecule fusing strategy
Discovery of 1-arylpyrrolidone derivatives as potent p53-MDM2 inhibitors based on molecule fusing strategy
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基于分子融合策略发现 1-芳基吡咯烷酮衍生物作为有效的 p53-MDM2 抑制剂
DOI：
10.1016/j.bmcl.2014.04.063
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发表时间：
2014-06-15
影响因子：
2.7
通讯作者：
Zhang, Wannian
中科院分区：
文献类型：
--
作者：
Li, Jin;Wu, Yuelin;Zhang, Wannian
通过分子融合策略将芳基引入到我们以前的吡咯烷酮支架上，得到了两组异丙醚-吡咯烷酮和α-苯乙胺-吡咯烷酮衍生物。后一系列中的两个新化合物8b和8g显示出较强的P53-MDM2抑制活性，其K-I值为90 nM，是母体化合物的3倍。我们还证实了化合物8b可以激活肺癌A549细胞中的P53蛋白。研究结果为进一步的引线优化提供了有价值的信息。(C)2014爱思唯尔有限公司。保留所有权利。
Introducing an aryl moiety to our previous pyrrolidone scaffold by molecule fusing strategy afforded two sets of isopropylether-pyrrolidone and alpha-phenylethylamine-pyrrolidone derivatives. Two novel compounds 8b and 8g of the latter serial showed potent p53-MDM2 inhibitory activities with K-i values of 90 nM which were three-time higher than that of the parent compound. We also confirmed compound 8b can activate p53 proteins in lung cancer A549 cells. The results offered us valuable information for further lead optimization. (C) 2014 Elsevier Ltd. All rights reserved.