3-[2-(acridin-9-ylamino)ethylamino]-N-(2-azidoethyl)propanamide | 1404199-55-8

• 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: 3-[2-(acridin-9-ylamino)ethylamino]-N-(2-azidoethyl)propanamide
• CAS: 1404199-55-8
• 化学式: C₂₀H₂₃N₇O
• 分子量: 377.449
• InChiKey: YBZGPVRPNPKDLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  80.4
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  、 3-[2-(acridin-9-ylamino)ethylamino]-N-(2-azidoethyl)propanamide 以 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成
  参考文献：
  名称：

  Using a Build-and-Click Approach for Producing Structural and Functional Diversity in DNA-Targeted Hybrid Anticancer Agents

  摘要：

  An efficient screening method was developed for functionalized DNA targeted platinum-containing hybrid anticancer agents based on metal mediated amine-to-nitrile addition, a form of "click" chemistry. The goal of the study was in generate platinum-acridine agents for their use as cytotoxic "warheads" in targeted and multifunctional therapies. This was achieved by introducing hydroxl, carboxylic acid, and azide functionalities in the acridine linker moiety and by varying the nonleaving groups attached to platinum. The assay, which was based on microscale reactions between 6 platinum-nitrile complexes and 10 acridine derivatives, yielded a small library of 60 platinum-acridines. Reactions were monitored, and product mixtures were quantitatively analyzed by automated in-line high-performance liquid chromatography-electrospray mass spectrometry (LC-ESMS) analysis and subjected to cell viability screening using a nonradioactive cell proliferation assay. The new prescreening methodology proves to be a powerful tool for establishing structure-activity relationships and for identifying target compounds.

  DOI：

  10.1021/jm301278c
• 作为产物：
  描述：

  N-苯基邻氨基苯甲酸 在 N,N'-羰基二咪唑 、 三氟乙酸 、 sodium hydroxide 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 3-[2-(acridin-9-ylamino)ethylamino]-N-(2-azidoethyl)propanamide
  参考文献：
  名称：

  使用 PCR 扩增 (DNA-ADAPT–qPCR) 后标记技术后的 DNA 加合物检测将前核糖体 RNA 基因鉴定为铂-吖啶抗癌剂的直接靶标

  摘要：

  铂吖啶试剂在癌细胞中造成的 DNA 损伤通过使用结合了点击化学 DNA 加合物的后标记、亲和下拉纯化和 PCR 扩增的检测方法进行了研究。该方法表明 rDNA 重复是混合试剂的细胞靶点，并且可能是药理学靶点。

  DOI：

  10.1002/chem.202102263

文献信息

• Using Fluorescent Post-Labeling To Probe the Subcellular Localization of DNA-Targeted Platinum Anticancer Agents
  作者：Song Ding、Xin Qiao、Jimmy Suryadi、Glen S. Marrs、Gregory L. Kucera、Ulrich Bierbach

  DOI：10.1002/anie.201210079

  日期：2013.3.18

  cells: A post‐labeling method was developed to image a DNA‐targeted platinum drug in cancer cells by confocal fluorescence microscopy. This was done using ligation chemistry between an azide‐functionalized platinum‐acridine anticancer drug and an alkyne‐modified dye, Alexa Fluor 488 (green star, see figure). The platinum‐acridine agent was shown to accumulate in the nucleoli of cancer cells (NCI‐H460)

  细胞周围的绿色：开发了一种标记后方法，通过共聚焦荧光显微镜对癌细胞中的 DNA 靶向铂药物进行成像。这是使用叠氮化物功能化铂-吖啶抗癌药物和炔改性染料 Alexa Fluor 488（绿色星形，见图）之间的连接化学完成的。铂-吖啶试剂被证明会在癌细胞 (NCI-H460) 的核仁中积聚。
• Targeted Delivery and Prodrug Designs for Platinum-Acridine Anti-Cancer Compounds and Methods Thereof
  申请人：Bierbach Ulrich

  公开号：US20140193334A1

  公开（公告）日：2014-07-10

  Acridine containing cisplatin compounds have been disclosed that show greater efficacy against cancer than other cisplatin compounds. Methods of delivery of those more effective cisplatin compounds to the nucleus in cancer cells is disclosed using one or more amino acids, one or more sugars, one or more polymeric ethers, C 1-6 alkylene-phenyl-NH—C(O)—R 15 , folic acid, α v β 3 integrin RGD binding peptide, tamoxifen, endoxifen, epidermal growth factor receptor, antibody conjugates, kinase inhibitors, diazoles, triazoles, oxazoles, erlotinib, and/or mixtures thereof; wherein R 15 is a peptide.

  披萨啤酒含有顺式铂类化合物，其对癌症的疗效比其他顺式铂类化合物更高。披萨啤酒使用一种或多种氨基酸、一种或多种糖、一种或多种聚醚、C1-6烷基苯基-NH—C(O)—R15、叶酸、αvβ3整合素RGD结合肽、他莫昔芬、恩多西芬、表皮生长因子受体、抗体偶联物、激酶抑制剂、咪唑、三唑、噁唑、厄洛替尼和/或其混合物来递送更有效的顺式铂类化合物到癌细胞核中。其中R15是一种肽。
• US9090640B2
  申请人：——

  公开号：US9090640B2

  公开（公告）日：2015-07-28
• Using a Build-and-Click Approach for Producing Structural and Functional Diversity in DNA-Targeted Hybrid Anticancer Agents
  作者：Song Ding、Xin Qiao、Gregory L. Kucera、Ulrich Bierbach

  DOI：10.1021/jm301278c

  日期：2012.11.26

  An efficient screening method was developed for functionalized DNA targeted platinum-containing hybrid anticancer agents based on metal mediated amine-to-nitrile addition, a form of "click" chemistry. The goal of the study was in generate platinum-acridine agents for their use as cytotoxic "warheads" in targeted and multifunctional therapies. This was achieved by introducing hydroxl, carboxylic acid, and azide functionalities in the acridine linker moiety and by varying the nonleaving groups attached to platinum. The assay, which was based on microscale reactions between 6 platinum-nitrile complexes and 10 acridine derivatives, yielded a small library of 60 platinum-acridines. Reactions were monitored, and product mixtures were quantitatively analyzed by automated in-line high-performance liquid chromatography-electrospray mass spectrometry (LC-ESMS) analysis and subjected to cell viability screening using a nonradioactive cell proliferation assay. The new prescreening methodology proves to be a powerful tool for establishing structure-activity relationships and for identifying target compounds.
• DNA Adduct Detection after Post‐Labeling Technique with PCR Amplification (DNA‐ADAPT–qPCR) Identifies the Pre‐ribosomal RNA Gene as a Direct Target of Platinum–Acridine Anticancer Agents
  作者：Xiyuan Yao、Ulrich Bierbach

  DOI：10.1002/chem.202102263

  日期：2021.10.21

  The DNA damage caused by a platinum–acridine agent in cancer cells was studied by using an assay that combines post-labeling of click chemistry-enabled DNA adducts, affinity pull-down purification, and PCR amplification. The method demonstrates that rDNA repeats are a cellular, and potentially pharmacological, target of the hybrid agents.

  铂吖啶试剂在癌细胞中造成的 DNA 损伤通过使用结合了点击化学 DNA 加合物的后标记、亲和下拉纯化和 PCR 扩增的检测方法进行了研究。该方法表明 rDNA 重复是混合试剂的细胞靶点，并且可能是药理学靶点。