3,4-dihydro-1-(2-phthalimidoethyl)isoquinoline | 127413-23-4

• 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: 3,4-dihydro-1-(2-phthalimidoethyl)isoquinoline
• 英文别名: N-[2-(3,4-Dihydro-1-isoquinolyl)ethyl]phthalimide；2-[2-(3,4-dihydroisoquinolin-1-yl)ethyl]isoindole-1,3-dione
• CAS: 127413-23-4
• 化学式: C₁₉H₁₆N₂O₂
• mdl: MFCD00552842
• 分子量: 304.348
• InChiKey: UFXJZIRGGNAHNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-1-(2-phthalimidoethyl)isoquinoline 在 盐酸 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 (+/-)-1-(2-aminoethyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  具有三氮杂甾醇相关结构的新型高能中间体类似物作为麦角固醇生物合成II的潜在抑制剂[1]。1,6,7,11b-Tetrahydro-2 H 嘧啶[4,3 - a ]异喹啉-4-胺作为新型8,13,15-三氮杂甾类化合物的母体化合物的合成优化

  摘要：

  有效合成1,6,7,11b-四氢-2 H- 嘧啶[4,3- a ]异喹啉-4-胺及其9-甲氧基衍生物的各种途径 ，被设计为稳定的三环三氮杂类似物研究了模拟麦角固醇生物合成的碳正离子高能中间体（HEI）的正电荷。从β-苯乙胺开始，制备了相应的3-氯 -N- 苯乙基丙酰胺，并将其转化为 N-苯乙基-3-邻苯二甲酰亚胺基丙酰胺 。这些酰胺经 Bischler-Napieralski 反应环化 ，在水解脱保护1-（氨基乙基）四氢异喹啉后产生。1,6,7,11b-四氢-2 H- 嘧啶基[4,3- 一个 ]异喹啉环系统然后通过与各种碳酸衍生物的双环二胺的缩合（二硫化碳，硝基胍，原碳酸四乙酯）建立。连同所施加的反应顺序，发生了意外的副反应。在同核和异核相关的1D和2D NMR实验的基础上，证明并完全指定了所有分离的化合物的结构。在 体外 与八个致病真菌标准面板的抗真菌敏感性试验揭示了pyrimidois

  DOI：

  10.1007/s00706-002-0559-7
• 作为产物：
  描述：

  3-(N-苯二甲酰亚氨基)丙酸 在 氯化亚砜 、 phosphorus pentoxide 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 21.5h， 生成 3,4-dihydro-1-(2-phthalimidoethyl)isoquinoline
  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

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。
• [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。
• US20140256767A1
  申请人：——

  公开号：US20140256767A1

  公开（公告）日：2014-09-11