1-methyl-3-bromo-4-(2-methyl-1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrroledione | 885701-91-7

• 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: 1-methyl-3-bromo-4-(2-methyl-1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrroledione
• 英文别名: 3-bromo-1-methyl-4-(2-methyl-1H-indol-3-yl)-maleimide；2-bromo-N-methyl-3-(2-methyl-1H-indol-3-yl)maleimide；3-bromo-1-methyl-4-(2-methyl-3-indolyl)maleimide；3-bromo-1-methyl-4-(2-methyl-1H-indol-3-yl)pyrrole-2,5-dione
• CAS: 885701-91-7
• 化学式: C₁₄H₁₁BrN₂O₂
• 分子量: 319.158
• InChiKey: NVWMXMIXEUDPJJ-UHFFFAOYSA-N

物化性质

• 熔点：
  160 °C (decomp)
• 沸点：
  484.2±45.0 °C(Predicted)
• 密度：
  1.685±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 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：

  1-methyl-3-bromo-4-(2-methyl-1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrroledione 、 二碳酸二叔丁酯 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 1.17h， 以80%的产率得到tert-butyl 3-(4-bromo-1-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-2-methyl-1H-indole-1-carboxylate
  参考文献：
  名称：

  On the use of diarylmaleimide derivatives in biological contexts: An investigation of the photochromic properties in aqueous solution

  摘要：

  A series of photochromic diarylmaleimide derivatives has been synthesized and studied with respect to the photochromic properties in aqueous solution. The main rationale is to investigate if these compounds could be used as photoswitchable units in biological contexts, motivated by the fact that the diarylmaleimide structural motif is identified in many pharmacophores. Thus, photoswitchable variants of this class of compounds could be very useful in the quest for photoactivatable drugs. The photoinduced cyclization reaction (colorization) is suppressed in solvents of high polarity, whereas the ring-opening reaction (decolorization) still occurs with high efficiency. The photochromically active anti-parallel conformer of the open form is more abundant in the asymmetrically substituted derivatives, which in turn favors the formation of the closed isomeric form. The rates of the thermal isomerization reactions have also been assessed, together with the resistance toward thermal degradation. Here it was observed that the maleimide derived compounds were not susceptible to the thermally driven reactions (hydrolysis and isomerization). (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.dyepig.2016.10.023
• 作为产物：
  描述：

  2-甲基吲哚 、 2,3-二溴-N-甲基马来酰亚胺 在 lithium hexamethyldisilazane 作用下， 以98%的产率得到1-methyl-3-bromo-4-(2-methyl-1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrroledione
  参考文献：
  名称：

  Efficient palladium-catalyzed synthesis of 3-aryl-4-indolylmaleimides

  摘要：

  开发出了用于 3-溴-1-甲基-4-(2-甲基-3-吲哚基)马来酰亚胺铃木偶联反应的改良型钯催化剂。在催化剂负载较低的情况下，芳基硼酸和杂芳基硼酸的偶联反应均能顺利进行，并获得良好甚至优异的产率。

  DOI：

  10.1039/b719160j

文献信息

• Catalytic and Stoichiometric Synthesis of Novel 3-Aminocarbonyl-, 3-Alkoxycarbonyl-, and 3-Amino-4-indolylmaleimides
  作者：Anne Brennführer、Helfried Neumann、Anahit Pews-Davtyan、Matthias Beller

  DOI：10.1002/ejoc.200800964

  日期：——

  Novel nonsymmetrically substituted 4-indolylmaleimides have been synthesized via palladium-catalyzed alkoxy- and aminocarbonylation of 3-bromo-1-methyl-4-(2-methyl-3-indolyl)maleimide (1) with alcohols and amines in the presence of carbon monoxide. The resulting carboxamide derivatives represent a new class of potentially bioactive compounds. In addition, the direct amination reaction of 1 proceeded

  在碳存在下，通过钯催化的烷氧基和氨基羰基化 3-溴-1-甲基-4-（2-甲基-3-吲哚基）马来酰亚胺（1）与醇和胺，合成了新型的非对称取代的 4-吲哚基马来酰亚胺一氧化氮。由此产生的甲酰胺衍生物代表了一类新的潜在生物活性化合物。此外，1 的直接胺化反应在没有催化剂的情况下顺利进行，并以良好的产率得到所需的 3-氨基-4-吲哚基马来酰亚胺。（© Wiley-VCH Verlag GmbH & Co. KGaA，69451 Weinheim，德国，2009）
• Use of maleimide derivatives for preventing and treating cancer
  申请人：CENTOGENE AG

  公开号：US10420754B2

  公开（公告）日：2019-09-24

  The present invention is related to a compound of formula (I): a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, a metabolite thereof or a prodrug thereof; for use in a method for the treatment and/or prevention of cancer, wherein X is selected from the group consisting of N—R1, O and S; R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkyl and hydrogen; R2 is selected from the group consisting of indolyl, substituted indolyl, azaindolyl and substituted azaindolyl; and R3 is selected from the group consisting of aryl, substituted aryl, unsubstituted heteroaryl, heterocyclyl and substituted heterocyclyl.

  本发明涉及一种式（I）化合物： 其药学上可接受的盐、其水合物、其溶液、其代谢物或其原药； 用于治疗和/或预防癌症的方法，其中 X选自由N-R1、O和S组成的组； R1 选自由烷基、环烷基、芳基、芳烷基和氢组成的组； R2 选自由吲哚基、取代的吲哚基、偶氮吲哚基和取代的偶氮吲哚基组成的组；和 R3 选自由芳基、取代的芳基、未取代的杂芳基、杂环基和取代的杂环基组成的组。
• 3-Bromo-4-(1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrroledione derivatives as new lead compounds for antibacterially active substances
  作者：Siavosh Mahboobi、Emerich Eichhorn、Alfred Popp、Andreas Sellmer、Sigurd Elz、Ute Möllmann

  DOI：10.1016/j.ejmech.2005.10.006

  日期：2006.2

  A number of new compounds containing 3-bromo-2,5-dihydro-1H-2,5-pyrroledione and indole substructures were found to have antibacterial activity against resistant strains of Staphylococcus aureus, Mycobacterium smegmatis and some other Gram positive bacteria. The investigated compounds exhibit minimal inhibition concentrations (MIC's) lower than those of ciprofloxacin, vancomycin and doxycycline resp. A different spectrum of activity, suggests a mechanism of action different to vancomycin and doxycycline. This might be important in circumventing existing resistance mechanisms. Here we report about the synthesis and on the antibacterial activity in a structure activity relationship study. (c) 2005 Elsevier SAS. All rights reserved.
• Novel indolylmaleimide acts as GSK-3β inhibitor in human neural progenitor cells
  作者：Anne-Caroline Schmöle、Anne Brennführer、Gnuni Karapetyan、Robert Jaster、Anahit Pews-Davtyan、Rayk Hübner、Stefanie Ortinau、Matthias Beller、Arndt Rolfs、Moritz J. Frech

  DOI：10.1016/j.bmc.2010.07.045

  日期：2010.9

  The Wnt pathway is involved in cellular processes linked to either proliferation or differentiation. Therefore small molecules offer an attractive opportunity to modulate this pathway, whereas the key enzyme GSK-3 beta is of special interest. In this study, non-symmetrically substituted indolylmaleimides have been synthesized and their ability to function as GSK-3 beta inhibitors has been investigated in a human neural progenitor cell line. Among the newly synthesized compounds, the substance IM-12 showed a significant activity in several biological tests which was comparable or even outplayed the effects of the known GSK-3 beta inhibitor SB-216763. Furthermore the treatment of human neural progenitor cells with IM-12 resulted in an increase of neuronal cells. Therefore we conclude that indolylmaleimides act via the canonical Wnt signalling pathway by inhibition of the key enzyme GSK-3 beta. (C) 2010 Elsevier Ltd. All rights reserved.
• 3-INDOLYL-4-PHENYL-1H-PYRROLE-2,5-DIONE DERIVATIVES AS INHIBITORS OF GLYCOGEN SYNTHASE KINASE-3BETA
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1307447A2

  公开（公告）日：2003-05-07