2-[2-(1,2,3,4-Tetrahydro-isoquinolin-1-yl)-ethyl]-isoindole-1,3-dione | 222022-67-5

• 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: 2-[2-(1,2,3,4-Tetrahydro-isoquinolin-1-yl)-ethyl]-isoindole-1,3-dione
• 英文别名: 2-[2-(1,2,3,4-tetrahydroisoquinolin-1-yl)ethyl]-2,3-dihydro-1H-isoindole-1,3-dione；2-[2-(1,2,3,4-tetrahydroisoquinolin-1-yl)ethyl]isoindole-1,3-dione
• CAS: 222022-67-5
• 化学式: C₁₉H₁₈N₂O₂
• 分子量: 306.364
• InChiKey: QZXVQOKDTLHPBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[2-(1,2,3,4-Tetrahydro-isoquinolin-1-yl)-ethyl]-isoindole-1,3-dione 在 碳酸氢钠 、 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand

  摘要：

  A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogues of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimising a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulphonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physico chemical properties, notably aqueous solubility. The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit I (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over mu and K opioid receptors. However the most active and selective compounds had poor aqueous solubility. Improved aqueous solubility was obtained by replacing the phthalimide group in I by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to I was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test, In the case of compound 19, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, 46, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, respectively, at a dose of 10 mmol/kg i.v.). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00017-7
• 作为产物：
  描述：

  3-(N-苯二甲酰亚氨基)丙酸 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三氯氧磷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 7.0h， 生成 2-[2-(1,2,3,4-Tetrahydro-isoquinolin-1-yl)-ethyl]-isoindole-1,3-dione
  参考文献：
  名称：

  [EN] DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS
  [FR] INHIBITEURS DIRECTS DE L'INTERACTION KEAP1-NRF2 EN TANT QUE MODULATEURS DE L'INFLAMMATION PAR ANTI-OXYDANT

  摘要：

  一种通过高通量筛选和引物开发将化合物识别为直接抑制Keap1-Nrf2相互作用的方法。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，且不受各种不良效应的影响，是潜在的化学预防和治疗剂的候选药物，可用于治疗涉及氧化应激和/或炎症的各种疾病或病症，包括但不限于癌症、糖尿病、阿尔茨海默病和帕金森病。还披露了识别新化合物和利用所识别的新化合物或含有这些化合物的组合物预防或治疗与Keap1-Nrf2相互作用活性相关的疾病或病症的方法。

  公开号：

  WO2013067036A1

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。
• US20140256767A1
  申请人：——

  公开号：US20140256767A1

  公开（公告）日：2014-09-11
• Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand
  作者：D.R. Barn、W.L. Caulfield、J. Cottney、K. McGurk、J.R. Morphy、Z. Rankovic、B. Roberts

  DOI：10.1016/s0968-0896(01)00017-7

  日期：2001.10

  A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogues of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimising a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulphonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physico chemical properties, notably aqueous solubility. The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit I (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over mu and K opioid receptors. However the most active and selective compounds had poor aqueous solubility. Improved aqueous solubility was obtained by replacing the phthalimide group in I by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to I was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test, In the case of compound 19, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, 46, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, respectively, at a dose of 10 mmol/kg i.v.). (C) 2001 Elsevier Science Ltd. All rights reserved.
• [EN] DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS<br/>[FR] INHIBITEURS DIRECTS DE L'INTERACTION KEAP1-NRF2 EN TANT QUE MODULATEURS DE L'INFLAMMATION PAR ANTI-OXYDANT
  申请人：UNIV RUTGERS

  公开号：WO2013067036A1

  公开（公告）日：2013-05-10

  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 Keapl-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.

  一种通过高通量筛选和引物开发将化合物识别为直接抑制Keap1-Nrf2相互作用的方法。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，且不受各种不良效应的影响，是潜在的化学预防和治疗剂的候选药物，可用于治疗涉及氧化应激和/或炎症的各种疾病或病症，包括但不限于癌症、糖尿病、阿尔茨海默病和帕金森病。还披露了识别新化合物和利用所识别的新化合物或含有这些化合物的组合物预防或治疗与Keap1-Nrf2相互作用活性相关的疾病或病症的方法。