5-isopropyl-8-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-isopropyl-8-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione
• 英文别名: 8-methyl-5-propan-2-yl-7,8-dihydro-6H-indeno[1,2-b]indole-9,10-dione
• 化学式: C₁₉H₁₉NO₂
• 分子量: 293.365
• InChiKey: AJIRSMPRRGVXEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  39.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-isopropyl-8-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 在 palladium on activated charcoal 作用下， 以 二苯醚 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Screening of indeno[1,2-b]indoloquinones by MALDI-MS: a new set of potential CDC25 phosphatase inhibitors brought to light

  摘要：

  Quinones and quinones-like compounds are potential candidates for the inhibition of CDC25 phosphatases. The combination of MALDI-MS analyses and biological studies was used to develop a rapid screening of a targeted library of indeno[1,2-b]indoloquinone derivatives. The screening protocol using MALDI-TOFMS and MALDI-FTICRMS highlighted four new promising candidates. Biological investigations showed that only compounds 5c-f inhibited CDC25A and -C phosphatases, with IC50 values around the micromolar range. The direct use of a screening method based on MALDI-MS technology allowed achieving fast scaffold identification of a new class of potent inhibitors of CDC25 phosphatases. These four molecules appeared as novel molecules of a new class of CDC25 inhibitors. Assessment of 5c-e in an MRC5 proliferation assay provided an early indicator of toxicity to mammalian cells. Compound 5d seems the most promising hit for developing new CDC25 inhibitors.

  DOI：

  10.1080/14756366.2016.1201480
• 作为产物：
  描述：

  4-甲基-环己烷-1,3-二酮 在 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 51.0h， 生成 5-isopropyl-8-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione
  参考文献：
  名称：

  Synthesis, Biological Evaluation and Molecular Modeling of Substituted Indeno[1,2-b]indoles as Inhibitors of Human Protein Kinase CK2

  摘要：

  由于其环状的6-5-5-6成员环结构，吲哚吲哚烯引起了人类CK2 ATP竞争性抑制剂设计的极大兴趣。本研究中，我们制备了二十一种吲哚[1,2-b]吲哚衍生物，并对它们进行了体外人类CK2的测试。吲哚吲哚酮5a和5b对人类CK2的抑制作用分别为IC50值0.17和0.61 µM。吲哚[1,2-b]吲哚醌7a在亚微摩尔范围内亦显示出对CK2的抑制活性（IC50 = 0.43 µM）。此外，还评估了大量吲哚吲哚烯衍生物对细胞系3T3、WI-38、HEK293T和MEF的细胞毒性活性。

  DOI：

  10.3390/ph8020279

文献信息

• Converting Potent Indeno[1,2-<i>b</i>]indole Inhibitors of Protein Kinase CK2 into Selective Inhibitors of the Breast Cancer Resistance Protein ABCG2
  作者：Gustavo Jabor Gozzi、Zouhair Bouaziz、Evelyn Winter、Nathalia Daflon-Yunes、Dagmar Aichele、Abdelhamid Nacereddine、Christelle Marminon、Glaucio Valdameri、Waël Zeinyeh、Andre Bollacke、Jean Guillon、Aline Lacoudre、Noël Pinaud、Silvia M. Cadena、Joachim Jose、Marc Le Borgne、Attilio Di Pietro

  DOI：10.1021/jm500943z

  日期：2015.1.8

  inhibition. The best ABCG2 inhibitors, such as 4c, 4h, 4i, 4j, and 4k, behaved as very weak inhibitors of CK2, whereas the most potent CK2 inhibitors, such as 4a, 4p, and 4e, displayed limited interaction with ABCG2. It was therefore possible to convert, through suitable substitutions of the indeno[1,2-b]indole-9,10-dione scaffold, potent CK2 inhibitors into selective ABCG2 inhibitors and vice versa. In addition

  合成了一系列茚并[1,2 - b ]吲哚-9,10-二酮衍生物作为人酪蛋白激酶II（CK2）抑制剂。最有效的抑制剂在C环上包含一个N 5-异丙基取代基。发现相同系列的化合物也可以抑制乳腺癌抗性蛋白ABCG2，但具有完全不同的结构-活性关系：N 5-苯乙基取代基很关键，D环的7或8位或在邻或间苯乙基位置的甲氧基也有抑制作用。最好的ABCG2抑制剂，例如4c，4h，4i，4j和4k，作为CK2的非常弱的抑制剂，而最有效的CK2抑制剂，如4a，4p和4e，与ABCG2的相互作用有限。因此，可以通过茚并[1,2 - b ]吲哚-9,10-二酮支架的适当取代，将有效的CK2抑制剂转化为选择性ABCG2抑制剂，反之亦然。另外，一些最好的ABCG2抑制剂表现出非常低的细胞毒性，因此具有很高的治疗率，并且似乎不被转运，构成了有希望进行进一步研究的候选药物。
• Synthesis, Biological Evaluation and Molecular Modeling of Substituted Indeno[1,2-b]indoles as Inhibitors of Human Protein Kinase CK2
  作者：Faten Alchab、Laurent Ettouati、Zouhair Bouaziz、Andre Bollacke、Jean-Guy Delcros、Christoph Gertzen、Holger Gohlke、Noël Pinaud、Mathieu Marchivie、Jean Guillon、Bernard Fenet、Joachim Jose、Marc Borgne

  DOI：10.3390/ph8020279

  日期：——

  Due to their system of annulated 6-5-5-6-membered rings, indenoindoles have sparked great interest for the design of ATP-competitive inhibitors of human CK2. In the present study, we prepared twenty-one indeno[1,2-b]indole derivatives, all of which were tested in vitro on human CK2. The indenoindolones 5a and 5b inhibited human CK2 with an IC50 of 0.17 and 0.61 µM, respectively. The indeno[1,2-b]indoloquinone 7a also showed inhibitory activity on CK2 at a submicromolar range (IC50 = 0.43 µM). Additionally, a large number of indenoindole derivatives was evaluated for their cytotoxic activities against the cell lines 3T3, WI-38, HEK293T and MEF.

  由于其环状的6-5-5-6成员环结构，吲哚吲哚烯引起了人类CK2 ATP竞争性抑制剂设计的极大兴趣。本研究中，我们制备了二十一种吲哚[1,2-b]吲哚衍生物，并对它们进行了体外人类CK2的测试。吲哚吲哚酮5a和5b对人类CK2的抑制作用分别为IC50值0.17和0.61 µM。吲哚[1,2-b]吲哚醌7a在亚微摩尔范围内亦显示出对CK2的抑制活性（IC50 = 0.43 µM）。此外，还评估了大量吲哚吲哚烯衍生物对细胞系3T3、WI-38、HEK293T和MEF的细胞毒性活性。
• Screening of indeno[1,2-<i>b</i>]indoloquinones by MALDI-MS: a new set of potential CDC25 phosphatase inhibitors brought to light
  作者：Faten Alchab、Estelle Sibille、Laurent Ettouati、Emilie Bana、Zouhair Bouaziz、Angélique Mularoni、Elodie Monniot、Denyse Bagrel、Joachim Jose、Marc Le Borgne、Patrick Chaimbault

  DOI：10.1080/14756366.2016.1201480

  日期：2016.11.3

  Quinones and quinones-like compounds are potential candidates for the inhibition of CDC25 phosphatases. The combination of MALDI-MS analyses and biological studies was used to develop a rapid screening of a targeted library of indeno[1,2-b]indoloquinone derivatives. The screening protocol using MALDI-TOFMS and MALDI-FTICRMS highlighted four new promising candidates. Biological investigations showed that only compounds 5c-f inhibited CDC25A and -C phosphatases, with IC50 values around the micromolar range. The direct use of a screening method based on MALDI-MS technology allowed achieving fast scaffold identification of a new class of potent inhibitors of CDC25 phosphatases. These four molecules appeared as novel molecules of a new class of CDC25 inhibitors. Assessment of 5c-e in an MRC5 proliferation assay provided an early indicator of toxicity to mammalian cells. Compound 5d seems the most promising hit for developing new CDC25 inhibitors.