benzo[a]pyrrolo[3,4-c]carbazole-1,3(2H,8H)-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: benzo[a]pyrrolo[3,4-c]carbazole-1,3(2H,8H)-dione
• 英文别名: benzo(a)pyrrolo(3,4-c)carbazole-1,3(2H,8H)-dione；4,14-diazapentacyclo[11.7.0.02,6.07,12.015,20]icosa-1(13),2(6),7,9,11,15,17,19-octaene-3,5-dione
• 化学式: C₁₈H₁₀N₂O₂
• 分子量: 286.29
• InChiKey: IUWAGZUDXHNNFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-(1H-吲哚-2-基)环己烷-1-醇 在 palladium on activated charcoal 盐酸 、 1-己烯 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 benzo[a]pyrrolo[3,4-c]carbazole-1,3(2H,8H)-dione
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel poly(ADP-ribose) polymerase-1 inhibitors

  摘要：

  A series of novel pyrrolocarbazoles was synthesized as potential PARP-1 inhibitors. Pyrrolocarbazole 1 was identified as a potent PARP-I inhibitor (IC50 = 36 nM) from our internal database. Synthesis of analogs around this template with the aid of modeling studies led to the identification of the truncated imide 14. Compound 14 (IC50 = 40 nM), with deleted B-ring, was found to be an equipotent PARP-1 inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.099

文献信息

• Design, Synthesis, and Biological Evaluation of 3,4-Diarylmaleimides as Angiogenesis Inhibitors
  作者：Christian Peifer、Thomas Stoiber、Eberhard Unger、Frank Totzke、Christoph Schächtele、Dieter Marmé、Ruth Brenk、Gerhard Klebe、Dieter Schollmeyer、Gerd Dannhardt

  DOI：10.1021/jm0580297

  日期：2006.2.1

  The new analogue 2 of combretastatin A-4 was discovered to be an inhibitor of tubulin polymerization with an IC50 of 7.6 microM and reduced angiogenesis in the in vivo chick embryo model. Interestingly, in a series of 2,3-diarylmaleimides closely related to this lead, no other compound was found to be active in the tubulin polymerization assay. However, by screening in the in vivo chick embryo assay

  发现康美他汀A-4的新类似物2是微管蛋白聚合的抑制剂，在体内鸡胚模型中的IC50为7.6 microM，并减少了血管生成。有趣的是，在一系列与该铅紧密相关的2，3-二芳基马来酰亚胺中，在微管蛋白聚合测定中未发现其他化合物具有活性。然而，通过在体内进行筛选，将雏鸡胚胎测定法10鉴定为有效的血管生成抑制剂，表明了另一种靶标。确实，分子建模研究表明在模型激酶CDK2的ATP结合位点有一个合理的10结合模式。根据这些结果，在10种类似的12种蛋白激酶中筛选了10种类似物的抑制活性，发现10种对VEGF-R2的高亲和力表明IC50为2.5 nM。
• Synthesis and Biological Evaluation of Novel Phenylcarbazoles as Potential Anticancer Agents
  作者：Sylvain Routier、Jean-Yves Mérour、Nathalie Dias、Amélie Lansiaux、Christian Bailly、Olivier Lozach、Laurent Meijer

  DOI：10.1021/jm050945x

  日期：2006.1.1

  We here report the synthesis and biological evaluation of new phenylcarbazole derivatives designed as potential anticancer agents. Indole and hydroxyindole were used to generate three scaffolds that were successively exploited to introduce various substituents on the maleimide moiety. The synthesis includes a final intramolecular key Heck-type reaction, which was carried out with a triflate derivative

  我们在这里报告了设计为潜在抗癌药的新苯基咔唑衍生物的合成和生物学评估。吲哚和羟基吲哚被用来产生三个支架，这些支架被连续利用以在马来酰亚胺部分上引入各种取代基。该合成包括最终的分子内键Heck型反应，该反应是用三氟甲磺酸酯衍生物或溴代苯基衍生物进行的。优化了每个步骤，并详细说明了完整的化学策略。几种化合物对CEM人白血病细胞显示出明显的细胞毒性，IC（50）值在10-100 nM范围内。描绘了精确的构效关系。评估了细胞周期分析，拓扑异构酶I抑制作用以及与DNA的相互作用，并研究了CDK活性的抑制作用。尽管药物与DNA的结合可能有助于细胞毒性作用，但仍未发现这些分子的确切分子靶标。本文报道的用于设计具有高度细胞毒性的化合物的有效化学路线为鉴定苯基咔唑系列抗肿瘤药提供了新的机会。
• Rhodium(III)-Catalyzed Dehydrogenative Annulation and Spirocyclization of 2-Arylindoles and 2-(1<i>H</i>-Pyrazol-1-yl)-1<i>H</i>-indoles with Maleimides: A Facile Access to Isogranulatimide Alkaloid Analogues
  作者：Vikki N. Shinde、Krishnan Rangan、Dalip Kumar、Anil Kumar

  DOI：10.1021/acs.joc.0c02467

  日期：2021.2.5

  A Rh(III)-catalyzed dehydrogenative annulation and spirocyclization of 2-arylindoles and 2-(1H-pyrazol-1-yl)-1H-indole with maleimides is described. The cascade protocol provided highly functionalized benzo[a]pyrrolo[3,4-c]carbazole-1,3(2H,8H)-diones and spiro[isoindolo[2,1-a]indole-6,3′-pyrrolidine]-2′,5′-diones in good to excellent. The developed reaction methodology exhibited broad substrate scope

  描述了Rh（III）催化的2-芳基吲哚和2-（1H-吡唑-1-基）-1H-吲哚与马来酰亚胺的脱氢环化和螺环化。级联方案提供了高度官能化的苯并[ a ]吡咯并[3,4- c ]咔唑-1,3（2 H，8 H）-二酮和螺[异吲哚并[ 2,1- a ]吲哚-6,3'-吡咯烷] -2'，5'-二烯良好。发达的反应方法具有广泛的底物范围和良好的官能团耐受性，并且操作简单且可扩展。研究了环状产物的光物理性质。2-（1 H-吡唑-1-基）-1 H的环状产物与2-苯基吲哚相比，-吲哚显示出高的吸收和发射值，并且具有大的红移。
• Oxidative cyclisations with palladium acetate. A short synthesis of staurosporine aglycone.
  作者：William Harris、Christopher H. Hill、Elizabeth Keech、Patrick Malsher

  DOI：10.1016/s0040-4039(00)61431-4

  日期：1993.12

  A palladium acetate mediated oxidative cyclisation has been used as the key step for the syntheses of staurosporine aglycone and related analogues.

  乙酸钯介导的氧化环化已被用作合成星形孢菌素糖苷配基和相关类似物的关键步骤。
• Synthesis of Aryl- and Heteroaryl[<i>a</i>]pyrrolo[3,4-<i>c</i>]carbazoles
  作者：Concha Sanchez-Martinez、Margaret M. Faul、Chuan Shih、Kevin A. Sullivan、John L. Grutsch、Jeremy T. Cooper、Stanley P. Kolis

  DOI：10.1021/jo034207x

  日期：2003.10.1

  Synthesis of aryl- and hetero[a]pyrrolo[3,4-c]carbazoles by photochemical oxidation and Heck cyclization are described. Photochemical oxidation of 2-naphthyl indolyl maleimide affords two different carbazole regioisomers, depending on the reaction conditions. The regiochemistry of the cyclization can be controlled using the Heck reaction.