2-(3-quinolinoyl)ethylamine | 101565-99-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(3-quinolinoyl)ethylamine
• 英文别名: 3-quinolinethaneamine；3-(1-amine-2-ethyl)quinoline；2-(Quinolin-3-YL)ethanamine；2-quinolin-3-ylethanamine
• CAS: 101565-99-5
• 化学式: C₁₁H₁₂N₂
• 分子量: 172.23
• InChiKey: QECIVNFEWUNEPX-UHFFFAOYSA-N

物化性质

• 沸点：
  380.8±22.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(3-quinolinoyl)ethylamine 在 氢氧化钾 、 羟胺 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 生成 (E)-N-hydroxy-3-[4-[(2-quinolin-3-ylethylamino)methyl]phenyl]prop-2-enamide
  参考文献：
  名称：

  N-Hydroxy-3-phenyl-2-propenamides as Novel Inhibitors of Human Histone Deacetylase with in Vivo Antitumor Activity:  Discovery of (2E)-N-Hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (NVP-LAQ824)

  摘要：

  A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC(50)s < 400 nM in a partially purified enzyme assay. However, potency in cell growth inhibition assays ranged over 2 orders of magnitude in two human carcinoma cell lines. Selected compounds having cellular IC50 < 750 nM were tested for maximum tolerated dose (MTD) and for efficacy in the HCT116 human colon tumor xenograft assay. Four compounds having an MTD 100 mg/kg were selected for dose-response studies in the HCT116 xenograft model. One compound, 9 (NVP-LAQ824), had significant dose-related activity in the HCT116 colon and A549 lung tumor models, high MTD, and low gross toxicity. On the basis, in part, of these properties, 9 has entered human clinical trials in 2002.

  DOI：

  10.1021/jm030235w
• 作为产物：
  描述：

  3-喹啉乙腈 在 palladium on activated charcoal 氢气 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 2-(3-quinolinoyl)ethylamine
  参考文献：
  名称：

  N-Hydroxy-3-phenyl-2-propenamides as Novel Inhibitors of Human Histone Deacetylase with in Vivo Antitumor Activity:  Discovery of (2E)-N-Hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (NVP-LAQ824)

  摘要：

  A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC(50)s < 400 nM in a partially purified enzyme assay. However, potency in cell growth inhibition assays ranged over 2 orders of magnitude in two human carcinoma cell lines. Selected compounds having cellular IC50 < 750 nM were tested for maximum tolerated dose (MTD) and for efficacy in the HCT116 human colon tumor xenograft assay. Four compounds having an MTD 100 mg/kg were selected for dose-response studies in the HCT116 xenograft model. One compound, 9 (NVP-LAQ824), had significant dose-related activity in the HCT116 colon and A549 lung tumor models, high MTD, and low gross toxicity. On the basis, in part, of these properties, 9 has entered human clinical trials in 2002.

  DOI：

  10.1021/jm030235w

文献信息

• Antineoplastic Agents. 603. Quinstatins: Exceptional Cancer Cell Growth Inhibitors
  作者：George R. Pettit、Noeleen Melody、Jean-Charles Chapuis

  DOI：10.1021/acs.jnatprod.6b01006

  日期：2017.3.24

  antibody drug conjugates (ADC). Among the first several hundred SAR products based on dolastatin 10 our group synthesized and termed auristatins was auristatin E (2a). An anticancer activity-equivalent, desmethylaurisatin E (2b), linked to a CD30 monoclonal antibody is the very successful anticancer drug Adcetris, now approved for use in 65 countries. In the present investigation, we discovered a new

  海兔Dolabella auricularia中包含的异常强大的抗癌药物dolastatin 10（1）的发现，为改善人类癌症的治疗打开了一个新的领域。随后，基于结构上修饰这种不寻常的天然肽同时保持制备成功的单克隆抗体药物偶联物（ADC）所需的显着抗癌活性的结果，取得了重大进展。在基于dolastatin 10的前几百种SAR产品中，我们小组合成并称为auristatin的是auristatin E（2a）。相当于抗癌活性的去甲基奥瑞沙汀E（2b）与CD30单克隆抗体相关联的是非常成功的抗癌药物Adcetris，现已批准在65个国家/地区使用。在本研究中，我们通过精心设计的喹啉取代C末端Doe单元，发现了新的auristatins子集，命名为dolastatin 10的quinstatins，从而导致低或亚纳摩尔水平的癌细胞生长抑制，这是化学上独特的构建所必需的。 ADC药物。喹他汀2-8的合成及其癌细胞系生物学数据均已介绍。
• [EN] QUINSTATIN COMPOUNDS<br/>[FR] COMPOSÉS QUINSTATINE
  申请人：PETTIT GEORGE ROBERT

  公开号：WO2017019489A1

  公开（公告）日：2017-02-02

  The present disclosure relates to Quinstatin compounds, pharmaceutical compositions comprising such compounds, kits, and methods for using such compounds or pharmaceutical compositions.

  本公开涉及Quinstatin化合物，包括这种化合物的药物组合物、试剂盒，以及使用这种化合物或药物组合物的方法。
• Method of Use of Deacetylase Inhibitors
  申请人：Izumo Seigo

  公开号：US20090012066A1

  公开（公告）日：2009-01-08

  The present invention provides methods of treating and/or preventing pathologic cardiac hypertrophy and heart failure comprising administering hydroxamate compounds which are deacetylase inhibitors.

  本发明提供了一种治疗和/或预防病理性心肌肥大和心力衰竭的方法，包括给予去乙酰化酶抑制剂的羟肟酸化合物。
• DEACETYLASE INHIBITORS
  申请人：Remiszewski Stacy William

  公开号：US20080176849A1

  公开（公告）日：2008-07-24

  The present invention provides hydroxamate compounds which are deacetylase inhibitors. The compounds are suitable for pharmaceutical compositions having anti-proliferative properties.

  本发明提供了一种羟肟酸化合物，其为去乙酰化酶抑制剂。这些化合物适用于具有抗增殖性质的药物组合物。
• Novel platelet-aggregation inhibitors
  申请人：MONSANTO COMPANY

  公开号：EP0454651A2

  公开（公告）日：1991-10-30

  Novel peptide mimetic compounds are provided which have useful activity as inhibitors of platelet aggregation. These compounds have the chemical structure wherein    x = 4 to 8,    y = 0 to 4,    W = CH₂-CH₂ or CH=CH,    Z = H, COOH, CONH₂, CH₂OH, CO₂R, CH₂OR or C₁₋₆ alkyl,    R = C₁₋₆ alkyl,    Ar = a nitrogen-containing heterocyclic group other than pyridyl, and    Asp = aspartic acid residue.

  本研究提供了新型肽模拟化合物，它们作为血小板聚集抑制剂具有有用的活性。这些化合物的化学结构如下 其中 x = 4 至 8 y = 0 至 4、 W = CH₂-CH₂ 或 CH=CH、 Z = H、COOH、CONH₂、CH₂OH、CO₂R、CH₂OR 或 C₁₋₆ 烷基、 R = C₁₋₆烷基、 Ar = 除吡啶基以外的含氮杂环基团，以及 Asp = 天冬氨酸残基。