3-(2-hydroxymethylphenyl)-2H-isoquinolin-1-one | 423150-36-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(2-hydroxymethylphenyl)-2H-isoquinolin-1-one
• 英文别名: 3-[2-(hydroxymethyl)phenyl]-2H-isoquinolin-1-one
• CAS: 423150-36-1
• 化学式: C₁₆H₁₃NO₂
• 分子量: 251.285
• InChiKey: FQGFQBFZUQZSPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(2-hydroxymethylphenyl)-2H-isoquinolin-1-one 在 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以51%的产率得到7H-异吲哚并[2,1-b]异喹啉-5-酮
  参考文献：
  名称：

  Structural modification of 3-arylisoquinolines to isoindolo[2,1-b]isoquinolinones for the development of novel topoisomerase 1 inhibitors with molecular docking study

  摘要：

  Isoindolo[2,1-b]isoquinolinones 9a-i were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular cyclization reaction. Among the synthesized compounds, 9d exhibited potent topoisomerase 1 inhibitory activity with cytotoxicities against three different tumor cell lines. A Surflex-dock docking study was performed to clarify the topoisomerase 1 inhibitory activity of 9d. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.042
• 作为产物：
  描述：

  3-[2-(4-methoxybenzyloxymethyl)phenyl]-2H-isoquinolin-1-one 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以89%的产率得到3-(2-hydroxymethylphenyl)-2H-isoquinolin-1-one
  参考文献：
  名称：

  Structural modification of 3-arylisoquinolines to isoindolo[2,1-b]isoquinolinones for the development of novel topoisomerase 1 inhibitors with molecular docking study

  摘要：

  Isoindolo[2,1-b]isoquinolinones 9a-i were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular cyclization reaction. Among the synthesized compounds, 9d exhibited potent topoisomerase 1 inhibitory activity with cytotoxicities against three different tumor cell lines. A Surflex-dock docking study was performed to clarify the topoisomerase 1 inhibitory activity of 9d. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.042

文献信息

• Antiviral Activity of Isoquinolone Derivatives against Influenza Viruses and Their Cytotoxicity
  作者：Yejin Jang、Jinhe Han、Xiaoli Li、Hyunjin Shin、Won-Jea Cho、Meehyein Kim

  DOI：10.3390/ph14070650

  日期：——

  Influenza viruses are one of the major causative agents for human respiratory infections. Currently, vaccines and antivirals approved for preventing and treating viral infections are available. However, limited protection efficacy and frequent emergence of drug-resistant viruses stand for a need for the development of antivirals with different chemical skeletons from existing drugs. Screening of a chemical library identified an isoquinolone compound (1) as a hit with 50% effective concentrations (EC50s) between 0.2 and 0.6 µM against the influenza A and B viruses. However, it exhibited severe cytotoxic effects with a 50% cytotoxic concentration (CC50) of 39.0 µM in canine kidney epithelial cells. To address this cytotoxic issue, we synthesized an additional 22 chemical derivatives. Through structure-activity, as well as structure-cytotoxicity relationship studies, we discovered compound 21 that has higher EC50 values ranging from 9.9 to 18.5 µM, but greatly alleviated cytotoxicity with a CC50 value over 300 µM. Mode-of-action and cell type-dependent antiviral experiments indicated that it targets viral polymerase activity and functions also in human cells. Here, we present a new class of viral polymerase inhibitors with a core skeleton of isoquinolone, of which antiviral activity could be better improved through following design and synthesis of its derivatives for drug development.

  流感病毒是人类呼吸道感染的主要致病因子之一。目前，已经批准用于预防和治疗病毒感染的疫苗和抗病毒药物已经问世。然而，现有药物的保护效果有限，且药物耐药病毒频繁出现，因此需要开发具有与现有药物不同化学骨架的抗病毒药物。对化学库的筛选确定了一种异喹啉类化合物（1）作为对甲型和乙型流感病毒的50%有效浓度（EC50）在0.2至0.6微米之间的抑制剂。然而，它在犬肾上皮细胞中表现出严重的细胞毒性效应，其50%细胞毒性浓度（CC50）为39.0微米。为解决这一细胞毒性问题，我们合成了另外22种化学衍生物。通过结构活性以及结构-细胞毒性关系研究，我们发现化合物21具有更高的EC50值，范围在9.9至18.5微米之间，但细胞毒性明显减轻，其CC50值超过300微米。作用模式和细胞类型相关的抗病毒实验表明，它靶向病毒聚合酶活性，同时在人类细胞中也发挥作用。在这里，我们提出一类具有异喹啉核心骨架的病毒聚合酶抑制剂，其抗病毒活性可以通过后续设计和合成其衍生物以用于药物开发而得到更好的改进。
• Structural modification of 3-arylisoquinolines to isoindolo[2,1-b]isoquinolinones for the development of novel topoisomerase 1 inhibitors with molecular docking study
  作者：Hue Thi My Van、Won-Jea Cho

  DOI：10.1016/j.bmcl.2009.03.042

  日期：2009.5

  Isoindolo[2,1-b]isoquinolinones 9a-i were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular cyclization reaction. Among the synthesized compounds, 9d exhibited potent topoisomerase 1 inhibitory activity with cytotoxicities against three different tumor cell lines. A Surflex-dock docking study was performed to clarify the topoisomerase 1 inhibitory activity of 9d. (C) 2009 Elsevier Ltd. All rights reserved.