2,3-dimethoxybenz[d]indeno[1,2-b]pyran-5,11-dione | 884902-25-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异香豆素及其衍生物
• 英文名称: 2,3-dimethoxybenz[d]indeno[1,2-b]pyran-5,11-dione
• 英文别名: 2,3-Dimethoxyindeno[1,2-c]isochromene-5,11-dione
• CAS: 884902-25-4
• 化学式: C₁₈H₁₂O₅
• 分子量: 308.29
• InChiKey: CCHIALXGDNFZST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-dimethoxybenz[d]indeno[1,2-b]pyran-5,11-dione 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 104.0h， 生成 bis-1,3-{(5,6-dihydro-5,11-diketo-2,3-dimethoxy-11H-indeno[1,2-c]isoquinoline)-6-propylamino}propane bis(trifluoroacetate)
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Bisindenoisoquinolines as Topoisomerase I Inhibitors

  摘要：

  The indenoisoquinolines represent a class of non-camptothecin topoisomerase I (Top1) inhibitors that exert cytotoxicity by trapping the covalent complex formed between DNA and Top1 during relaxation of DNA supercoils. As an ongoing evaluation of Top1 inhibition and anticancer activity, indenoisoquinolines were linked via their lactam side chains to provide polyamines end-capped with intercalating motifs. The resulting bisindenoisoquinolines were evaluated for cytotoxicity in the National Cancer Institute's human cancer cell screen and for Top1 inhibition. Preliminary findings suggested that the 2-3-2and 3-3-3 linkers, referring to the number of carbons between nitrogen atoms, were optimal for both potent Top1 inhibition and cytotoxicity. Using optimized linkers, bisindenoisoquinolines were synthesized with nitro and methoxy substituents on the aromatic rings. The biological results for substituted compounds revealed a disagreement between the structure-activity relationships of monomeric indenoisoquinolines and bisindenoisoquinolines as Top1 inhibitors, but cytotoxicity was maintained for both series of compounds.

  DOI：

  10.1021/jm060046o
• 作为产物：
  描述：

  2-甲酰基-4.5-二甲氧基-苯甲酸 在 sodium methylate 、 对甲苯磺酸 作用下， 以 甲醇 、 乙酸乙酯 、 苯 为溶剂， 反应 34.0h， 生成 2,3-dimethoxybenz[d]indeno[1,2-b]pyran-5,11-dione
  参考文献：
  名称：

  Synthesis of benz[d]indeno[1,2-b]pyran-5,11-diones: Versatile intermediates for the design and synthesis of topoisomerase I inhibitors

  摘要：

  A method has been developed that relies on a two-step, one-pot condensation between phthalide and 2-carboxybenzaldehydes to provide benz[a]indeno[ 1,2-h]pyran-5,11-diones in a multi-gram fashion. Treatment of these compounds with a primary amine allows rapid access to various N-substituted indenoisoquinolines, whose in vitro anticancer activity and topoisomerase I inhibition have been evaluated. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.008

文献信息

• Alcohol-, Diol-, and Carbohydrate-Substituted Indenoisoquinolines as Topoisomerase I Inhibitors: Investigating the Relationships Involving Stereochemistry, Hydrogen Bonding, and Biological Activity
  作者：Katherine E. Peterson、Maris A. Cinelli、Andrew E. Morrell、Akhil Mehta、Thomas S. Dexheimer、Keli Agama、Smitha Antony、Yves Pommier、Mark Cushman

  DOI：10.1021/jm101338z

  日期：2011.7.28

  topoisomerase I (Top1) can be inhibited by heterocyclic compounds such as indolocarbazoles and indenoisoquinolines. Carbohydrate and hydroxyl-containing side chains are essential for the biological activity of indolocarbazoles. The current study investigated how similar functionalities could be “translated” to the indenoisoquinoline system and how stereochemistry and hydrogen bonding affect biological

  DNA松弛酶拓扑异构酶I（Top1）可以被杂环化合物如吲哚并咔唑和茚并异喹啉抑制。碳水化合物和含羟基的侧链对于吲哚并咔唑的生物活性是必不可少的。目前的研究调查了如何将相似的功能“转化”到茚并异喹啉系统，以及立体化学和氢键如何影响生物活性。本文描述了用短链醇、二醇和碳水化合物取代的茚并异喹啉的制备和测定。几种化合物（包括那些来自糖的化合物）显示出有效的 Top1 中毒和抗增殖活性。二醇取代的茚并异喹啉的 Top1 中毒活性取决于立体化学。虽然效果惊人，由于配体和 Top1-DNA 复合物之间类似的计算相互作用以及结合模式的模糊性，分子建模和对接研究没有表明活性差异的任何原因。还观察到碳水化合物衍生的茚并异喹啉具有立体化学依赖性。尽管在其他类别的 Top1 抑制剂中观察到了类似的趋势，但这种效应的确切性质尚未阐明。
• N-Substituted Indenoisoquinolines and Syntheses Thereof
  申请人：Cushman Mark S.

  公开号：US20080318995A1

  公开（公告）日：2008-12-25

  N-Substituted indenoisoquinoline compounds, and pharmaceutical formulations of N-substituted indenoisoquinoline compounds are described. Also described are processes for preparing N-substituted indenoisoquinoline compounds. Also described are methods for treating cancer in mammals using the described N-substituted indenoisoquinoline compounds or pharmaceutical formulations thereof.

  本发明涉及N-取代的茚并异喹啉化合物及其制备方法，以及N-取代的茚并异喹啉化合物的药物制剂。同时，还描述了制备N-取代的茚并异喹啉化合物的方法。本发明还涉及使用所述的N-取代的茚并异喹啉化合物或其药物制剂治疗哺乳动物癌症的方法。
• N-substituted indenoisoquinolines and syntheses thereof
  申请人：Cushman Mark S.

  公开号：US20120101119A1

  公开（公告）日：2012-04-26

  N-Substituted indenoisoquinoline compounds, and pharmaceutical formulations of N-substituted indenoisoquinoline compounds are described. Also described are processes for preparing N-substituted indenoisoquinoline compounds. Also described are methods for treating cancer in mammals using the described N-substituted indenoisoquinoline compounds or pharmaceutical formulations thereof.

  本发明涉及N-取代吲哚异喹啉化合物及其药物制剂。还描述了制备N-取代吲哚异喹啉化合物的过程。还描述了使用所述N-取代吲哚异喹啉化合物或其药物制剂治疗哺乳动物癌症的方法。
• N-SUBSTITUTED INDENOISOQUINOLINES AND SYNTHESES THEREOF
  申请人：CUSHMAN Mark S.

  公开号：US20140336188A1

  公开（公告）日：2014-11-13

  N-Substituted indenoisoquinoline compounds, and pharmaceutical formulations of N-substituted indenoisoquinoline compounds are described. Also described are processes for preparing N-substituted indenoisoquinoline compounds. Also described are methods for treating cancer in mammals using the described N-substituted indenoisoquinoline compounds or pharmaceutical formulations thereof.

  本文描述了N-取代吲哚异喹啉化合物及其药物配方，并描述了制备N-取代吲哚异喹啉化合物的过程。同时，本文还描述了使用所述N-取代吲哚异喹啉化合物或其药物配方治疗哺乳动物癌症的方法。
• A PROCESS FOR PREPARING N-SUBSTITUTED INDENOISOQUINOLINES
  申请人：Purdue Research Foundation

  公开号：EP3112349A2

  公开（公告）日：2017-01-04

  A process for preparing a compound of the formula without isolating an intermediate product, the process comprising: reacting a compound of the formula with a compound of the formula and cyclizing the intermediate product.

  一种制备式化合物的工艺 不分离中间产物的制备方法，该方法包括 与一种式化合物反应 和 环化中间产物。