(2'RS)-5,6-dihydro-6-[(2',3'-dihydroxypropyl)]-5,11-dioxo-11H-indeno[1,2-c]isoquinoline | 1313588-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (2'RS)-5,6-dihydro-6-[(2',3'-dihydroxypropyl)]-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
• 英文别名: 6-(2,3-Dihydroxypropyl)indeno[1,2-c]isoquinoline-5,11-dione
• CAS: 1313588-99-6
• 化学式: C₁₉H₁₅NO₄
• 分子量: 321.332
• InChiKey: BBHXBKGHEJSVFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2'RS)-5,6-dihydro-6-[(2',3'-dihydroxypropyl)]-5,11-dioxo-11H-indeno[1,2-c]isoquinoline 在 4-二甲氨基吡啶 、 四丙基高钌酸铵 、 N-甲基吗啉氧化物 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 22.5h， 生成 5,6-dihydro-6-[2'-oxo-3'-(tert-butyldiphenylsilyloxy)propyl]-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  醇、二醇和碳水化合物取代的茚并异喹啉作为拓扑异构酶 I 抑制剂：研究涉及立体化学、氢键和生物活性的关系

  摘要：

  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。

  DOI：

  10.1021/jm101338z
• 作为产物：
  描述：

  2-(2-Carboxyphenyl)-1,3-indandion 在 溴 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 60.0h， 生成 (2'RS)-5,6-dihydro-6-[(2',3'-dihydroxypropyl)]-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  Synthesis and cytotoxic evaluation of novel indenoisoquinoline-propan-2-ol hybrids

  摘要：

  The synthesis of N-substituted indenoisoquinolines was performed by applying a two-step condensation between 2-carboxybenzaldehyde and phthalide, followed by treatment with various primary amines. N-allylindenoisoquinoline was subsequently selected as a substrate for hydroxybromination, providing 6-(3-bromo-2-hydroxy)indenoisoquinoline as a key intermediate for derivatization in the lactam side chain. In this way, a series of 6-(2-hydroxypropyl)indenoisoquinolines bearing various functional groups at the 3'-position were prepared, which can be considered as novel indenoisoquinoline-propan-2-ol hybrid molecules. Subsequent cytotoxic evaluation of 28 indenoisoquinolines against two human cancer cell lines (Hep-G2 and KB) demonstrated a moderate to high antiproliferative activity displayed by 11 indenoisoquinolines thus synthesized. In particular, the introduction of the 2-hydroxypropyl side chain was shown to be beneficial for the overall cytotoxic activity, pointing to the potential relevance of these novel indenoisoquinoline-propan-2-ol hybrids. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2015.12.045

文献信息

• [EN] ALCOHOL-, DIOL-, AND CARBOHYDRATE-SUBSTITUTED INDENOISOQUINOLINES AS TOPOISOMERASE I INHIBITORS<br/>[FR] INDÉNO-ISOQUINOLÉINES À SUBSTITUTION ALCOOL, DIOL ET HYDRATE DE CARBONE UTILISÉES EN TANT QU'INHIBITEURS DE LA TOPOISOMÉRASE
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2012162513A3

  公开（公告）日：2013-03-28
• ALCOHOL-, DIOL-, AND CARBOHYDRATE-SUBSTITUTED INDENOISOQUINOLINES AS TOPOISOMERASE I INHIBITORS
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：US20150148370A1

  公开（公告）日：2015-05-28

  The invention described herein pertains to substituted indenoisoquinoline compounds as described herein, wherein R A , R D , W, X and Y are defined herein, pharmaceutical compositions and formulations comprising the indenoisoquinoline compounds, their synthesis, and methods for their use in the treatment and/or prevention of cancer.
• US9328073B2
  申请人：——

  公开号：US9328073B2

  公开（公告）日：2016-05-03
• US9682990B2
  申请人：——

  公开号：US9682990B2

  公开（公告）日：2017-06-20
• Synthesis and cytotoxic evaluation of novel indenoisoquinoline-propan-2-ol hybrids
  作者：Tham Pham Thi、Lena Decuyper、Tan Luc Quang、Chinh Pham The、Tuyet Anh Dang Thi、Ha Thanh Nguyen、Thuy Giang Le Nhat、Tra Nguyen Thanh、Phuong Hoang Thi、Matthias D’hooghe、Tuyen Van Nguyen

  DOI：10.1016/j.tetlet.2015.12.045

  日期：2016.1

  The synthesis of N-substituted indenoisoquinolines was performed by applying a two-step condensation between 2-carboxybenzaldehyde and phthalide, followed by treatment with various primary amines. N-allylindenoisoquinoline was subsequently selected as a substrate for hydroxybromination, providing 6-(3-bromo-2-hydroxy)indenoisoquinoline as a key intermediate for derivatization in the lactam side chain. In this way, a series of 6-(2-hydroxypropyl)indenoisoquinolines bearing various functional groups at the 3'-position were prepared, which can be considered as novel indenoisoquinoline-propan-2-ol hybrid molecules. Subsequent cytotoxic evaluation of 28 indenoisoquinolines against two human cancer cell lines (Hep-G2 and KB) demonstrated a moderate to high antiproliferative activity displayed by 11 indenoisoquinolines thus synthesized. In particular, the introduction of the 2-hydroxypropyl side chain was shown to be beneficial for the overall cytotoxic activity, pointing to the potential relevance of these novel indenoisoquinoline-propan-2-ol hybrids. (C) 2015 Elsevier Ltd. All rights reserved.