6-(4-methoxybenzyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione | 281223-41-4

• 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: 6-(4-methoxybenzyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione
• 英文别名: 6-(4-methoxybenzyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione；6-[(4-Methoxyphenyl)methyl]indeno[1,2-c]isoquinoline-5,11-dione
• CAS: 281223-41-4
• 化学式: C₂₄H₁₇NO₃
• 分子量: 367.404
• InChiKey: IMGVSGXCKOGKMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(4-methoxybenzyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione 、 己基溴化镁 以 四氢呋喃 、 二丁醚 为溶剂， 反应 12.0h， 以98%的产率得到11-hexyl-11-hydroxy-6-(4-methoxybenzyl)-6H,11H-indeno[1,2-c]isoquinolin-5-one
  参考文献：
  名称：

  Indeno[1,2-c]isoquinolines as enhancing agents on all-trans retinoic acid-mediated differentiation of human myeloid leukemia cells

  摘要：

  Induction of differentiation is a new and promising approach to cancer therapy, well illustrated by the treatment of acute myeloid leukemia with all-trans retinoic acid (ATRA). Using combination of ATRA and chemotherapy, adverse effects such as retinoic acid syndrome have decreased, and long-term survival has improved. In this study, we demonstrated that the indeno[1,2-c]isoquinolines markedly enhanced differentiation of human myeloid leukemia HL-60 and NB4 cells when simultaneously combined with a low dose of ATRA. Of the tested compounds, 6-(4-methoxybenzyl)-2,11-dimethyl-6H, 11H-indeno[1,2-c]isoquinolin-5-one (IIQ-16), an indeno[1,2-c]isoquinoline derivative, showed the highest differentiation-enhancing activity via a pathway involved with protein kinase C, extracellular signal-regulated kinase, and e-Jun N-terminal kinase. The ability to enhance the differentiation potential of ATRA by IIQ-16 may improve outcomes in the therapy of acute promyelocytic leukemia. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.086
• 作为产物：
  描述：

  2-[(三甲基硅基)乙炔基]苯甲酸甲酯 在 selenium(IV) oxide 、 1,1'-双(二苯基膦)二茂铁 、 CoI₂(1,1’-bis(diphenylphosphino)ferrocene) 、 zinc(II) chloride 、 锌 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 68.0h， 生成 6-(4-methoxybenzyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione
  参考文献：
  名称：

  钴催化邻卤代苯二胺与炔烃的双重环化：一条通往生物活性茚并异喹啉酮的有力途径

  摘要：

  已开发了钴催化的双环化反应，用于由2-溴苯甲醛，胺和2-（乙炔基）苯甲酸甲酯合成各种取代的茚并异喹啉酮。该方法也可以用于合成高度功能化的生物活性茚并异喹啉酮及其衍生物。提出了钴催化的一种可能机理，包括由溴苯甲醛和胺形成亚胺，然后进行一系列的氧化加成，炔烃插入，环化反应以及碳-碳双键迁移。区域选择性炔烃的插入对于第二次成环的成功起着重要作用。

  DOI：

  10.1002/chem.201501152

文献信息

• Cobalt-Catalyzed Dual Annulation of<i>o</i>-Halobenzaldimine with Alkyne: A Powerful Route toward Bioactive Indenoisoquinolinones
  作者：Chuan-Che Liu、Jen-Chieh Hsieh、Rajendra Prasad Korivi、Chien-Hong Cheng

  DOI：10.1002/chem.201501152

  日期：2015.6.22

  A cobalt‐catalyzed dual annulation reaction for the synthesis of variously substituted indenoisoquinolinones from 2‐bromobenzaldehydes, amines, and methyl 2‐(ethynyl)benzoates has been developed. This method could also be applied to the synthesis of an array of highly functionalized bioactive indenoisoquinolinones and their derivatives. A possible mechanism of the cobalt catalysis is proposed, involving

  已开发了钴催化的双环化反应，用于由2-溴苯甲醛，胺和2-（乙炔基）苯甲酸甲酯合成各种取代的茚并异喹啉酮。该方法也可以用于合成高度功能化的生物活性茚并异喹啉酮及其衍生物。提出了钴催化的一种可能机理，包括由溴苯甲醛和胺形成亚胺，然后进行一系列的氧化加成，炔烃插入，环化反应以及碳-碳双键迁移。区域选择性炔烃的插入对于第二次成环的成功起着重要作用。
• Indeno[1,2-c]isoquinolines as enhancing agents on all-trans retinoic acid-mediated differentiation of human myeloid leukemia cells
  作者：Seung Hyun Kim、Sang Mi Oh、Ju Han Song、Daeho Cho、Quynh Manh Le、Suh–Hee Lee、Won-Jea Cho、Tae Sung Kim

  DOI：10.1016/j.bmc.2007.10.086

  日期：2008.2.1

  Induction of differentiation is a new and promising approach to cancer therapy, well illustrated by the treatment of acute myeloid leukemia with all-trans retinoic acid (ATRA). Using combination of ATRA and chemotherapy, adverse effects such as retinoic acid syndrome have decreased, and long-term survival has improved. In this study, we demonstrated that the indeno[1,2-c]isoquinolines markedly enhanced differentiation of human myeloid leukemia HL-60 and NB4 cells when simultaneously combined with a low dose of ATRA. Of the tested compounds, 6-(4-methoxybenzyl)-2,11-dimethyl-6H, 11H-indeno[1,2-c]isoquinolin-5-one (IIQ-16), an indeno[1,2-c]isoquinoline derivative, showed the highest differentiation-enhancing activity via a pathway involved with protein kinase C, extracellular signal-regulated kinase, and e-Jun N-terminal kinase. The ability to enhance the differentiation potential of ATRA by IIQ-16 may improve outcomes in the therapy of acute promyelocytic leukemia. (c) 2007 Elsevier Ltd. All rights reserved.