5-isopropyl-7-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione | 1018687-10-9

• 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-7-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione
• 英文别名: 7-methyl-5-propan-2-yl-7,8-dihydro-6H-indeno[1,2-b]indole-9,10-dione
• CAS: 1018687-10-9
• 化学式: C₁₉H₁₉NO₂
• 分子量: 293.365
• InChiKey: KLZHCUVZHUIBOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 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-7-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 在 palladium 10% on activated carbon 作用下， 以 二苯醚 为溶剂， 反应 3.0h， 以70%的产率得到9-hydroxy-5-isopropyl-7-methyl-5H-indeno[1,2-b]indol-10-one
  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
• 作为产物：
  描述：

  5-甲基环己烷-1,3-二酮 在 N,N,N',N'-Tetraisopropylsulfinyldiamin 、 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-7-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

• Partially Saturated Indeno[1,2-<i>b</i>]indole Derivatives via Deoxygenation of Heterocyclic α-Hydroxy-<i>N</i>,<i>O</i>-hemiaminals
  作者：Hans-Jörg Hemmerling、Guido Reiss

  DOI：10.1055/s-0028-1087983

  日期：——

  A series of 3-aminocyclohex-2-enones were reacted with indane-1,2,3-trione monohydrate (ninhydrin) yielding 4b,9b-dihydroxyindeno[1,2-b]indoles that were deoxygenated to indeno[1,2-b]indoles.

  一系列3-氨基环己烯-2-酮与单水合的吡喃-1,2,3-三酮（呋喃啉）反应，生成4b,9b-二羟基吲哚[1,2-b]吲哚，其后经脱氧反应转化为吲哚[1,2-b]吲哚。
• SUBSTITUTED INDENO[1,2-B]INDOLE DERIVATIVES AS NOVEL INHIBITORS OF PROTEIN KINASE CK2 AND THEIR USE AS TUMOR THERAPEUTIC AGENTS, CYTOSTATICS AND DIAGNOSTIC AIDS
  申请人：Hemmerling Hans-Jorg

  公开号：US20100056599A1

  公开（公告）日：2010-03-04

  Synthesis of novel substituted indeno[1,2-b]indole derivatives of the type of 5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-diones and 5H-indeno[1,2-b]indole-6,9,10-triones, which show pronounced inhibition of the human protein kinase CK2, and the use thereof as active ingredients in medicaments and/or drug products in particular for the treatment of neoplastic diseases.

  合成新型取代的indeno[1,2-b]indole衍生物，包括5,6,7,8-四氢indeno[1,2-b]indole-9,10-二酮和5H-indeno[1,2-b]indole-6,9,10-三酮。这些衍生物表现出显著的抑制人类蛋白激酶CK2的作用，并可作为药物中的活性成分，特别用于治疗肿瘤性疾病。
• QSAR Model of Indeno[1,2-b]indole Derivatives and Identification of N-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-b]furan-3-carboxamide as a Potent CK2 Inhibitor
  作者：Samer Haidar、Christelle Marminon、Dagmar Aichele、Abdelhamid Nacereddine、Wael Zeinyeh、Abdeslem Bouzina、Malika Berredjem、Laurent Ettouati、Zouhair Bouaziz、Marc Le Borgne、Joachim Jose

  DOI：10.3390/molecules25010097

  日期：——

  was used to predict the activity of 25 compounds with naphtho[2,3-b]furan-4,9-dione derivatives, which were previously predicted as CK2 inhibitors via a molecular modeling approach. The activities of four naphtho[2,3-b]furan-4,9-dione derivatives were determined in vitro and one of them (N-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxamide) turned out to inhibit CK2 with an IC50

  酪蛋白激酶 II (CK2) 是一种深入研究的酶，涉及不同的疾病，尤其是癌症。不同的支架被用来开发这种酶的抑制剂。在这里，我们报告了 20 种酚类、酮类和对醌类茚并 [1,2-b] 吲哚衍生物作为 CK2 抑制剂的合成和生物学评价。活性最强的化合物是 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4h 和 1,3-dibromo-5-isopropyl-5， 6,7,8-四氢茚并[1,2-b]indole-9,10-dione 4w，IC50 值为0.11 µM。此外，还开发了基于茚并[1,2-b]吲哚结构的 QSAR 模型。该模型用于预测 25 种含有萘并[2,3-b]呋喃-4,9-二酮衍生物的化合物的活性，这些化合物之前通过分子建模方法被预测为 CK2 抑制剂。体外测定了四种萘并[2,3-b]呋喃-4
• 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.
• US8133913B2
  申请人：——

  公开号：US8133913B2

  公开（公告）日：2012-03-13