4-chloro-3-(5-bromo-1H-indol-3-yl)-1-phenyl-1H-pyrrole-2,5-dione | 959418-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 4-chloro-3-(5-bromo-1H-indol-3-yl)-1-phenyl-1H-pyrrole-2,5-dione
• 英文别名: 3-chloro-4-(5-bromo-1H-indol-3-yl)-1-phenyl-2,5-pyrroledione；3-chloro-4-(5-bromo-1H-indol-3-yl)-1-phenyl-1H-pyrrole-2,5-dione；3-(5-bromo-1H-indol-3-yl)-4-chloro-1-phenyl-1H-pyrrole-2,5-dione；3-(5-bromo-1H-indol-3-yl)-4-chloro-1-phenylpyrrole-2,5-dione
• CAS: 959418-01-0
• 化学式: C₁₈H₁₀BrClN₂O₂
• 分子量: 401.647
• InChiKey: LYXDTBNWWIYSHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-3-(5-bromo-1H-indol-3-yl)-1-phenyl-1H-pyrrole-2,5-dione 在 氨 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 以70.5%的产率得到3-(5-bromo-1H-indol-3-yl)-4-chloropyrrole-2,5-dione
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 3-Chloro-4-(indol-3-yl)-2,5- pyrroledione Derivatives as Antitumor Agents

  摘要：

  合成了一系列3-氯-4-(吲哚-3-基)-2,5-吡咯二酮衍生物，并评估其对五种人癌细胞系（K562、A549、ECA-109、KB和SMMC-7721）的体外细胞毒性活性。大多数化合物表现出强效的细胞毒性，IC50值在低微摩尔范围内。结果表明，吡咯二酮环上3位的氯原子的存在对活性至关重要。化合物6a是最有效的（IC50：0.67∼3.93 μM），将成为进一步开发新型抗肿瘤药物的有前景的模板。

  DOI：

  10.2174/1570180811310050003
• 作为产物：
  描述：

  5-溴吲哚 、 2,3-二氯-N-苯基马来酰亚胺 在 乙基溴化镁 作用下， 以 乙醚 、 苯 、 四氢呋喃 为溶剂， 生成 4-chloro-3-(5-bromo-1H-indol-3-yl)-1-phenyl-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  3-芳基-4-吲哚基-马来酰亚胺作为强效突变体异柠檬酸脱氢酶-1抑制剂的合成和生物学评估。

  摘要：

  通过高通量筛选和基于结构的优化，获得了一系列具有新颖结构的3-芳基-4-吲哚基马来酰亚胺IDH1 / R132H抑制剂。大多数化合物（例如7a，7d，7h，7i，7k和7o）对IDH1 / R132H表现出高抑制作用，并且对IDH1 / WT，IDH2 / WT，GDH，GK和FBP具有高度选择性。在细胞水平上对生物学活性和功能的评价表明，化合物7h，7i和7k可以有效抑制表达IDH1 / R132H的U87MG细胞中2-羟基戊二酸的产生。此外，IDH1 / R132H的过表达可能会导致7h逆转髓样白血病细胞系TF-1的分化阻滞。我们还根据实验数据探索了结构-活性关系，以期为将来的研究铺平道路。

  DOI：

  10.1016/j.bmc.2018.12.029

文献信息

• Synthesis, Cytotoxicity and Protein Kinase C Inhibition of Arylpyrrolylmaleimides
  作者：Gui-Qing Xu、Chong Zhang、Lei Zhang、Xing-Lu Zhou、Bo Yang、Qiao-Jun He、Yong-Zhou Hu

  DOI：10.1002/ardp.200700190

  日期：2008.5

  novel arylpyrrolylmaleimides was synthesized and evaluated for their in‐vitro cytotoxicity against various human cancer cell lines and their protein‐kinase C inhibitory activity. Some of the compounds showed high or moderate cytotoxic activity against the tested cell lines. Compound 6b is the most promising compound against the tested cancer cell lines; 6d and 6e showed moderate protein‐kinase C inhibition

  合成了一系列新型芳基吡咯基马来酰亚胺，并评估了它们对各种人类癌细胞系的体外细胞毒性及其蛋白激酶 C 抑制活性。一些化合物对测试的细胞系显示出高或中度的细胞毒活性。化合物 6b 是最有前途的抗癌细胞系化合物；6d和6e显示出中度蛋白激酶C抑制。根据获得的实验数据讨论结构 - 活性关系。
• Synthesis and Cytotoxicity of Indolopyrrolemaleimides
  作者：Gui-Qing Xu、Peng Guo、Chong Zhang、Qiao-Jun He、Bo Yang、Yong-Zhou Hu

  DOI：10.1248/cpb.55.1302

  日期：——

  A series of indolopyrrolemaleimides have been synthesized and evaluated for their cytotoxicity in vitro against human leukemia cell line and four human solid cancer cell lines. Some of the compounds showed high or mediate activity against the lines. 6dc is the most promising compound among them. The inhibition toward topoisomerase I was also studied.

  我们合成了一系列吲哚吡咯马来酰亚胺化合物，并在体外评估了它们对人类白血病细胞系和四种人类实体癌细胞系的细胞毒性。其中一些化合物对这些细胞系表现出很高的活性或介导活性。6dc 是其中最有前途的化合物。此外，还研究了 6dc 对拓扑异构酶 I 的抑制作用。
• Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3β (GSK-3β) inhibitors
  作者：Qing Ye、Guiqing Xu、Dan Lv、Zhe Cheng、Jia Li、Yongzhou Hu

  DOI：10.1016/j.bmc.2009.05.031

  日期：2009.7

  A series of novel 4-azaindolyl-indolyl-maleimides were synthesized and evaluated for their GSK-3 beta inhibitory activity. Most compounds exhibited high potency to GSK-3 beta. Among them, compound 7c was the most promising GSK-3 beta inhibitor. Preliminary structure-activity relationships were discussed based on the experimental data obtained and showed that different substituents on the indole ring and side chains at 1-position of indole had varying degrees of influence on the GSK-3 beta inhibitory potency. In a cell-based functional assay, compounds 7c and 15a significantly reduced A beta-induced Tau hyperphosphorylation by inhibiting GSK-3 beta. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of 3-aryl-4-indolyl-maleimides as potent mutant isocitrate dehydrogenase-1 inhibitors
  作者：Xiaoqi Liu、Yuanyuan Hu、Anhui Gao、Meng Xu、Lixin Gao、Lei Xu、Yubo Zhou、Jianrong Gao、Qing Ye、Jia Li

  DOI：10.1016/j.bmc.2018.12.029

  日期：2019.2

  A series of 3-aryl-4-indolylmaleimide IDH1/R132H inhibitors with a novel structure was obtained by high-throughput screening and structure-based optimization. Most compounds such as 7a, 7d, 7h, 7i, 7k and 7o showed high inhibitory effects on IDH1/R132H and were highly selective against IDH1/WT, IDH2/WT, GDH, GK, and FBP. Evaluation of the biological activities and function at cellular level showed

  通过高通量筛选和基于结构的优化，获得了一系列具有新颖结构的3-芳基-4-吲哚基马来酰亚胺IDH1 / R132H抑制剂。大多数化合物（例如7a，7d，7h，7i，7k和7o）对IDH1 / R132H表现出高抑制作用，并且对IDH1 / WT，IDH2 / WT，GDH，GK和FBP具有高度选择性。在细胞水平上对生物学活性和功能的评价表明，化合物7h，7i和7k可以有效抑制表达IDH1 / R132H的U87MG细胞中2-羟基戊二酸的产生。此外，IDH1 / R132H的过表达可能会导致7h逆转髓样白血病细胞系TF-1的分化阻滞。我们还根据实验数据探索了结构-活性关系，以期为将来的研究铺平道路。
• Synthesis and Biological Evaluation of 3-Chloro-4-(indol-3-yl)-2,5- pyrroledione Derivatives as Antitumor Agents
  作者：Yuchen Lin、Jing Chen

  DOI：10.2174/1570180811310050003

  日期：2013.4.1

  A series of 3-chloro-4-(indol-3-yl)-2,5-pyrroledione derivatives were synthesized and evaluated for their cytotoxic activities in vitro against five human cancer cell lines (K562, A549, ECA-109, KB and SMMC-7721). Most compounds displayed potent cytotoxicity with IC50 values in low micromolar range. The results showed that the existence of the chlorine atom at 3-position on the pyrroledione ring was crucial for the activity. Compound 6a, the most potent one (IC50: 0.67∼3.93 μM), would be a promising template for further development of novel antitumor agents

  合成了一系列3-氯-4-(吲哚-3-基)-2,5-吡咯二酮衍生物，并评估其对五种人癌细胞系（K562、A549、ECA-109、KB和SMMC-7721）的体外细胞毒性活性。大多数化合物表现出强效的细胞毒性，IC50值在低微摩尔范围内。结果表明，吡咯二酮环上3位的氯原子的存在对活性至关重要。化合物6a是最有效的（IC50：0.67∼3.93 μM），将成为进一步开发新型抗肿瘤药物的有前景的模板。