10-methyl-3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione | 68724-96-9

• 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: 10-methyl-3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione
• 英文别名: 10-methyl-3,4-dihydro-2H-azepino[3,4-b]indole-1,5-dione
• CAS: 68724-96-9
• 化学式: C₁₃H₁₂N₂O₂
• 分子量: 228.25
• InChiKey: FJLAKIVHVGAJHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  51.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  10-methyl-3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione 在 sodium hydride 、 sodium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 2-benzyl-10-methyl-1-oxo-1,2,3,10-tetrahydroazepino[3,4-b]indol-5-yl trifluoromethanesulfonate
  参考文献：
  名称：

  Azepino [3,4- b ]吲哚-5-基三氟甲烷磺酸酯的合成及反应活性

  摘要：

  5-取代的氮杂并[3,4的合成的便利方法b ]吲哚-1-酮18 - 27进行说明。该合成是基于关键中间体氮杂[3,4- b ]吲哚-5-基三氟甲磺酸盐3的钯介导的交叉偶联反应，该中间体是从相应的氮杂[3,4- b ]吲哚-1,5-二酮中获得的。4。

  DOI：

  10.1016/s0040-4020(00)00374-4
• 作为产物：
  描述：

  吲哚-2-羧酸 在 4-二甲氨基吡啶 、 lithium hydroxide 、 phosphorus pentoxide 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 67.0h， 生成 10-methyl-3,4-dihydroazepino[3,4-b]indole-1,5(2H,10H)-dione
  参考文献：
  名称：

  Azepino [3,4- b ]吲哚-5-基三氟甲烷磺酸酯的合成及反应活性

  摘要：

  5-取代的氮杂并[3,4的合成的便利方法b ]吲哚-1-酮18 - 27进行说明。该合成是基于关键中间体氮杂[3,4- b ]吲哚-5-基三氟甲磺酸盐3的钯介导的交叉偶联反应，该中间体是从相应的氮杂[3,4- b ]吲哚-1,5-二酮中获得的。4。

  DOI：

  10.1016/s0040-4020(00)00374-4

文献信息

• Synthesis of 4-substituted azepino[3,4-b]indole-1,5-diones
  作者：Julien Perron、Benoı̂t Joseph、Jean-Yves Mérour

  DOI：10.1016/s0040-4020(03)00979-7

  日期：2003.8

  Mono- or dibromo derivatives 2 and 3 were prepared by an efficient two-step route from 10-methyl-azepino[3,4-b]indole-1,5-dione 1. Elimination reaction on 2 gave access to 4-bromo-10-methyl-2H,10H-azepino[3,4-b]indole-1,5-diones 4. Finally, 4-substituted 10-methyl-2H,10H-azepino[3,4-b]indole-1,5-diones 6–14 were synthesised in good yields from 4 via palladium-mediated cross-coupling reactions.

  单或二溴衍生物2和3是通过有效的两步路线从10-甲基-氮杂环庚烷[3,4- b ]吲哚-1,5-二酮1制备的。在2上进行消除反应可得到4-溴-10-甲基-2 H，10 H-氮杂环庚烷[3,4- b ]吲哚-1,5-二酮4。最后，4-取代的10-甲基- 2 ħ，10 ħ -azepino [3,4 b ]吲哚-1,5-二酮6 - 14是在从良好的收率合成4通过钯介导的交叉偶联反应。
• Synthesis and evaluation of novel anti-proliferative pyrroloazepinone and indoloazepinone oximes derived from the marine natural product hymenialdisine
  作者：Alex W. White、Nicholas Carpenter、Jerome R.P. Lottin、Richard A. McClelland、Robert I. Nicholson

  DOI：10.1016/j.ejmech.2012.08.022

  日期：2012.10

  properties. The synthesis and biological evaluation of a novel series of pyrroloazepinone and indoloazepinone oximes is reported. These compounds showed promising growth inhibition activity against four human cancer cell lines but did not significantly inhibit the cell cycle regulator cyclin dependent kinase 2. The most active compounds in this series displayed improved anti-proliferative activity over the

  四氢a庚酮药效基团是许多有趣的化合物的组成部分，包括几种具有抗癌特性的海洋天然产物。报道了一系列新的吡咯并ze庚酮和吲哚并ze庚酮肟的合成和生物学评价。这些化合物对四种人类癌细胞系显示出有希望的生长抑制活性，但并未显着抑制细胞周期调节剂细胞周期蛋白依赖性激酶2。该系列中最具活性的化合物显示出比相关的合成吲哚并西平kenpaullone更高的抗增殖活性。氮杂环庚烷药效团显示的结构活性关系表明了用于抗癌药物发现的几种新的先导化合物。
• Preparation of hymenialdisine derivatives and use thereof
  申请人：Board of Trustees of Michigan State University

  公开号：US20040235820A1

  公开（公告）日：2004-11-25

  The synthesis and biological activity of indoloazepines and acid amine salts thereof which are structurally related to naturally-occurring hymenialdisine is disclosed. Naturally-occurring hymenialdisine obtained from the sponge is a potent inhibitor of production of cytokines interleukin-2 (IL-2) and tumor necrosis factor-&agr; (TNF-&agr;). The chemically-synthesized indoloazepines of the invention also inhibit production of IL-2 and TNF-&agr;. The indoloazepines are useful for treating inflammatory diseases, particularly diseases associated with kinases NF-&kgr;B or GSK-3&bgr; activation or NF-&kgr;B activated gene expression products. The indoloazepines are useful for the treatment of cancer by the inhibition of kinases CHK1 and CHK2.

  本文披露了与天然存在的海绵素结构相关的吲哚环庚烷和其酸胺盐的合成和生物活性。从海绵获得的天然存在的海绵素是细胞因子白细胞介素-2（IL-2）和肿瘤坏死因子-α（TNF-α）产生的有效抑制剂。发明的化学合成的吲哚环庚烷也抑制IL-2和TNF-α的产生。这些吲哚环庚烷对治疗炎症性疾病特别有效，尤其是与激酶NF-κB或GSK-3β激活或NF-κB激活的基因表达产物相关的疾病。这些吲哚环庚烷通过抑制激酶CHK1和CHK2对癌症的治疗也是有效的。
• Inhibition of Cytokine Production by Hymenialdisine Derivatives
  作者：Vasudha Sharma、Theresa A. Lansdell、Guangyi Jin、Jetze J. Tepe

  DOI：10.1021/jm040013d

  日期：2004.7.1

  We describe herein the synthesis and biological activity of two indoloazepines that are structurally related to the marine sponge metabolite hymenialdisine. The natural product hymenialdisine was found to be a potent inhibitor of interleukin-2 (IC50 = 2.4 muM) and tumor necrosis factor alpha (IC50 = 1.4 muM) production. One of the hymenialdisine derived indoloazepines was found to also inhibit interleukin-2 (IC50 = 3.5 muM) and tumor necrosis factor alpha (IC50 = 8.2 muM) production.
• Access to ring-fused azepino[3,4-b]indole-1,5-dione derivatives by ring-closing olefin metathesis
  作者：Julien Perron、Benoît Joseph、Jean-Yves Mérour

  DOI：10.1016/j.tet.2004.07.069

  日期：2004.10

  The new ring-fused azepino[5,6-b]indole derivatives 3, 4 and 5 were prepared from diene precursors 8, 9, 13 and 15 in fair yields via a final ring-closing olefin metathesis. (C) 2004 Elsevier Ltd. All rights reserved.