5-(dimethylamino)-3-(4-methoxyphenyl)isoquinolin-1(2H)-one | 203628-19-7

• 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: 5-(dimethylamino)-3-(4-methoxyphenyl)isoquinolin-1(2H)-one
• 英文别名: 5-(dimethylamino)-3-(4-methoxyphenyl)-2H-isoquinolin-1-one
• CAS: 203628-19-7
• 化学式: C₁₈H₁₈N₂O₂
• 分子量: 294.353
• InChiKey: IUSKLVVMANREKI-UHFFFAOYSA-N

物化性质

• 沸点：
  548.9±50.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(dimethylamino)-3-(4-methoxyphenyl)isoquinolin-1(2H)-one 在 potassium carbonate 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 3-(4-methoxyphenyl)-N,N-dimethyl-1-(4-methylpiperazin-1-yl)isoquinolin-5-amine
  参考文献：
  名称：

  Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3-arylisoquinoline derivatives

  摘要：

  In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r(2) as high as 0.721) was obtained through CoMFA, (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)80019-9
• 作为产物：
  描述：

  4-甲氧基苯甲腈 、 3-dimethylamino-2-methyl-N,N-dimethylbenzamide 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.0h， 以53%的产率得到5-(dimethylamino)-3-(4-methoxyphenyl)isoquinolin-1(2H)-one
  参考文献：
  名称：

  Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3-arylisoquinoline derivatives

  摘要：

  In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r(2) as high as 0.721) was obtained through CoMFA, (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)80019-9

文献信息

• 3-ARYL-5-SUBSTITUTED-ISOQUINOLIN-1-ONE COMPOUNDS AND THEIR THERAPEUTIC USE
  申请人：INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

  公开号：US20150099732A1

  公开（公告）日：2015-04-09

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2H-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.

  本发明通常涉及治疗化合物领域。更具体地，本发明涉及某些3-芳基-5-取代-2H-异喹啉-1-酮化合物，该化合物在抑制PARP（例如PARP1，TNKS1，TNKS2等）和/或Wnt信号传导方面具有作用。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物，在体内和体外，来抑制PARP（例如PARP1，TNKS1，TNKS2等）；抑制Wnt信号传导；治疗通过抑制PARP（例如PARP1，TNKS1，TNKS2等）改善的疾病；治疗通过抑制Wnt信号传导改善的疾病；治疗癌症等增生症状。
• [EN] 3-ARYL-5-SUBSTITUTED-ISOQUINOLIN-1-ONE COMPOUNDS AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS DE 3-ARYLISOQUINOL-1-ONE 5-SUBSTITUÉE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：CANCER RES INST ROYAL

  公开号：WO2015036759A1

  公开（公告）日：2015-03-19

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted- 2/-/-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc. Formula (I)

  本发明涉及治疗化合物领域。更具体地，本发明涉及某些3-芳基-5-取代-2/-/-异喹啉-1-酮化合物，该化合物在抑制PARP（例如PARP1、TNKS1、TNKS2等）和/或Wnt信号传导方面具有作用。本发明还涉及包含此类化合物的药物组合物，以及使用这些化合物和组合物在体外和体内抑制PARP（例如PARP1、TNKS1、TNKS2等）；抑制Wnt信号传导；治疗通过抑制PARP（例如PARP1、TNKS1、TNKS2等）改善的疾病；治疗通过抑制Wnt信号传导改善的疾病；治疗增生性疾病如癌症等。公式（I）
• 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。
• Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents
  作者：Won-Jea Cho、Myun-Ji Park、Byung-Ho Chung、Chong-Ok Lee

  DOI：10.1016/s0960-894x(97)10190-1

  日期：1998.1

  To investigate the structure-activity relationship of 7,8-dimethoxy-2-methyl-3-(4,5-methylenedioxy-2-vinylphenyl)isoquinolin-1(2H)-one 2, diverse substituted 3-arylisoquinolines were synthesized and tested in vitro antitumor activity against five human tumor cell lines. The results showed a broad antitumor spectrum for a series of 3-arylisoquinolines. (C) 1997 Elsevier Science Ltd. All rights reserved.
• US9193689B2
  申请人：——

  公开号：US9193689B2

  公开（公告）日：2015-11-24