N-(6,7-dimethoxy-3,4-dihydro-isoquinolin-1-ylmethyl)-phthalimide | 32672-60-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-(6,7-dimethoxy-3,4-dihydro-isoquinolin-1-ylmethyl)-phthalimide
• 英文别名: N-(6,7-dimethoxy-3,4-dihydro-[1]isoquinolylmethyl)-phthalimide；N-(6,7-Dimethoxy-3,4-dihydro-[1]isochinolylmethyl)-phthalimid；2-[(6,7-Dimethoxy-3,4-dihydroisoquinolin-1-yl)methyl]isoindole-1,3-dione
• CAS: 32672-60-9
• 化学式: C₂₀H₁₈N₂O₄
• 分子量: 350.374
• InChiKey: RDQNFLPQBQIKNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(6,7-dimethoxy-3,4-dihydro-isoquinolin-1-ylmethyl)-phthalimide 在 甲醇 、 sodium tetrahydroborate 、 碳酸氢钠 、 溶剂黄146 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 3.0h， 生成 3-(2-(2-fluorophenyl)-2-oxoethylidene)-9,10-dimethoxy-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one
  参考文献：
  名称：

  3-Aroylmethylene-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-ones as Potent Nrf2/ARE Inducers in Human Cancer Cells and AOM-DSS Treated Mice

  摘要：

  Nrf2-mediated activation of ARE regulates expression of cytoprotective enzymes against oxidative stress, inflammation, and carcinogenesis. We have discovered a novel structure (1) as an ARE inducer via luciferase reporter assay to screen the in-house database of our laboratory. The potency of 1 was evaluated by the expression of NQO-1, HO-1, and nuclear translocation of Nrf2 in HCT116 cells. In vivo potency of 1 was studied using AOM-DSS models, showing that the development of colorectal adenomas was significantly inhibited. Administration with 1 lowered the expression of IL-6, IL-1 beta, and promoted Nrf2 nuclear translocation. These results indicated that 1 is a potent Nrf2/ARE activator, both in vitro and in vivo. Forty-one derivatives were synthesized for SAR study, and a more potent compound 17 was identified. To our knowledge, this is a potent ARE activator. Besides, its novel structure makes it promising for further optimization.

  DOI：

  10.1021/jm400944k
• 作为产物：
  描述：

  2-氯-N-(2-(3,4-二甲氧基苯基)乙基)乙酰胺 在 四磷十氧化物 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 14.0h， 生成 N-(6,7-dimethoxy-3,4-dihydro-isoquinolin-1-ylmethyl)-phthalimide
  参考文献：
  名称：

  3-Aroylmethylene-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-ones as Potent Nrf2/ARE Inducers in Human Cancer Cells and AOM-DSS Treated Mice

  摘要：

  Nrf2-mediated activation of ARE regulates expression of cytoprotective enzymes against oxidative stress, inflammation, and carcinogenesis. We have discovered a novel structure (1) as an ARE inducer via luciferase reporter assay to screen the in-house database of our laboratory. The potency of 1 was evaluated by the expression of NQO-1, HO-1, and nuclear translocation of Nrf2 in HCT116 cells. In vivo potency of 1 was studied using AOM-DSS models, showing that the development of colorectal adenomas was significantly inhibited. Administration with 1 lowered the expression of IL-6, IL-1 beta, and promoted Nrf2 nuclear translocation. These results indicated that 1 is a potent Nrf2/ARE activator, both in vitro and in vivo. Forty-one derivatives were synthesized for SAR study, and a more potent compound 17 was identified. To our knowledge, this is a potent ARE activator. Besides, its novel structure makes it promising for further optimization.

  DOI：

  10.1021/jm400944k

文献信息

• DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS
  申请人：Rutgers, The State University of New Jersey

  公开号：US20180148408A1

  公开（公告）日：2018-05-31

  A method of identifying compounds as direct inhibitors of Keap1-Nrf2 interaction through high-throughput screening and lead development. The direct inhibitors of Keap1-Nrf2 interaction are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential drug candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, and Parkinson's. Novel compounds are identified and methods of preventing or treating diseases or conditions related to Keap1-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.

  通过高通量筛选和引物开发的方法，识别化合物作为Keap1-Nrf2相互作用的直接抑制剂。Keap1-Nrf2相互作用的直接抑制剂比现有的间接抑制剂更具特异性，不受各种不良影响，并且是化学预防和治疗各种涉及氧化应激和/或炎症的疾病或症状的潜在药物候选者，包括但不限于癌症、糖尿病、阿尔茨海默病和帕金森病。还公开了识别新化合物以及使用所识别的新化合物或含有这些化合物的组合物来预防或治疗与Keap1-Nrf2相互作用活性相关的疾病或症状的方法。
• Isoquinoline Derivatives. II. Synthesis of 1-Aminomethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  作者：H. J. Harwood、T. B. Johnson

  DOI：10.1021/ja01337a048

  日期：1933.10
• Yamazaki, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1959, vol. 79, p. 1003,1006
  作者：Yamazaki

  DOI：——

  日期：——
• 3-Aroylmethylene-2,3,6,7-tetrahydro-1<i>H</i>-pyrazino[2,1-<i>a</i>]isoquinolin-4(11b<i>H</i>)-ones as Potent Nrf2/ARE Inducers in Human Cancer Cells and AOM-DSS Treated Mice
  作者：Mei-yang Xi、Jian-min Jia、Hao-peng Sun、Zhong-ying Sun、Jie-wei Jiang、Ya-jing Wang、Min-ye Zhang、Jun-feng Zhu、Li-li Xu、Zheng-yu Jiang、Xin Xue、Ming Ye、Xi Yang、Yuan Gao、Lei Tao、Xiao-ke Guo、Xiao-li Xu、Qing-long Guo、Xiao-jin Zhang、Rong Hu、Qi-dong You

  DOI：10.1021/jm400944k

  日期：2013.10.24

  Nrf2-mediated activation of ARE regulates expression of cytoprotective enzymes against oxidative stress, inflammation, and carcinogenesis. We have discovered a novel structure (1) as an ARE inducer via luciferase reporter assay to screen the in-house database of our laboratory. The potency of 1 was evaluated by the expression of NQO-1, HO-1, and nuclear translocation of Nrf2 in HCT116 cells. In vivo potency of 1 was studied using AOM-DSS models, showing that the development of colorectal adenomas was significantly inhibited. Administration with 1 lowered the expression of IL-6, IL-1 beta, and promoted Nrf2 nuclear translocation. These results indicated that 1 is a potent Nrf2/ARE activator, both in vitro and in vivo. Forty-one derivatives were synthesized for SAR study, and a more potent compound 17 was identified. To our knowledge, this is a potent ARE activator. Besides, its novel structure makes it promising for further optimization.