N-(acridin-9-yl)-N′-methylpropane-1,3-diamine | 86863-21-0

• 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: N-(acridin-9-yl)-N′-methylpropane-1,3-diamine
• 英文别名: N-acridin-9-yl-N'-methylpropane-1,3-diamine；N-9-Acridinyl-N'-methyl-1,3-propanediamine；N'-acridin-9-yl-N-methylpropane-1,3-diamine
• CAS: 86863-21-0
• 化学式: C₁₇H₁₉N₃
• 分子量: 265.358
• InChiKey: SGCRIYMGLGMMSV-UHFFFAOYSA-N

物化性质

• 沸点：
  472.9±30.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  、 N-(acridin-9-yl)-N′-methylpropane-1,3-diamine 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以459 mg的产率得到[PtCl(en)(C22H26N4O2)]NO3
  参考文献：
  名称：

  Synthesis, Aqueous Reactivity, and Biological Evaluation of Carboxylic Acid Ester-Functionalized Platinum–Acridine Hybrid Anticancer Agents

  摘要：

  The synthesis of platinum-acridine hybrid agents containing carboxylic acid ester groups is described. The most active derivatives and the unmodified parent compounds showed up to 6-fold higher activity in ovarian cancer (OVCAR-3) and breast cancer (MCF-7, MDA-MB-231) cell lines than cisplatin. Inhibition of cell proliferation at nanomolar concentrations was observed in pancreatic (PANC-1) and nonsmall cell lung cancer cells (NSCLC, NCI-H460) of 80- and 150-fold, respectively. Introduction of the ester groups did not affect the cytotoxic properties of the hybrids, which form the same monofunctional-intercalative DNA adducts as the parent compounds, as demonstrated in a plasmid unwinding assay. In-line high-performance liquid chromatography and electrospray mass spectrometry (LC-ESMS) shows that the ester moieties undergo platinum-mediated hydrolysis in a chloride concentration-dependent manner to form carboxylate chelates. Potential applications of the chloride-sensitive ester hydrolysis as a self-immolative release mechanism for tumor-selective delivery of platinum-acridines are discussed.

  DOI：

  10.1021/jm300879k
• 作为产物：
  描述：

  9-phenoxyacridine 在 盐酸 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 N-(acridin-9-yl)-N′-methylpropane-1,3-diamine
  参考文献：
  名称：

  双（ac啶基硫脲）铂（II）配合物：胶质母细胞瘤细胞的合成，DNA亲和力和生物活性。

  摘要：

  报道了两种新颖的双（r啶）铂（II）配合物的制备。带电荷的4+结合物可能通过双嵌入与双链天然DNA（K（i）> 10（6））强烈结合。细胞活力测定用于证明两种化合物均能在SNB19脑肿瘤细胞中以微摩尔浓度介导细胞毒性。

  DOI：

  10.1016/s0960-894x(02)01078-8

文献信息

• 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。
• 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.
• US9090640B2
  申请人：——

  公开号：US9090640B2

  公开（公告）日：2015-07-28
• Synthesis, Aqueous Reactivity, and Biological Evaluation of Carboxylic Acid Ester-Functionalized Platinum–Acridine Hybrid Anticancer Agents
  作者：Leigh A. Graham、Jimmy Suryadi、Tiffany K. West、Gregory L. Kucera、Ulrich Bierbach

  DOI：10.1021/jm300879k

  日期：2012.9.13

  The synthesis of platinum-acridine hybrid agents containing carboxylic acid ester groups is described. The most active derivatives and the unmodified parent compounds showed up to 6-fold higher activity in ovarian cancer (OVCAR-3) and breast cancer (MCF-7, MDA-MB-231) cell lines than cisplatin. Inhibition of cell proliferation at nanomolar concentrations was observed in pancreatic (PANC-1) and nonsmall cell lung cancer cells (NSCLC, NCI-H460) of 80- and 150-fold, respectively. Introduction of the ester groups did not affect the cytotoxic properties of the hybrids, which form the same monofunctional-intercalative DNA adducts as the parent compounds, as demonstrated in a plasmid unwinding assay. In-line high-performance liquid chromatography and electrospray mass spectrometry (LC-ESMS) shows that the ester moieties undergo platinum-mediated hydrolysis in a chloride concentration-dependent manner to form carboxylate chelates. Potential applications of the chloride-sensitive ester hydrolysis as a self-immolative release mechanism for tumor-selective delivery of platinum-acridines are discussed.
• Bis(acridinylthiourea)platinum(II) complexes: synthesis, DNA affinity, and biological activity in glioblastoma cells
  作者：Todd M Augustus、Joel Anderson、Suzanne M Hess、Ulrich Bierbach

  DOI：10.1016/s0960-894x(02)01078-8

  日期：2003.3

  The preparation of two novel bis(acridine)platinum(II) complexes is reported. The 4+ charged conjugates associate strongly with double-stranded native DNA (K(i)>10(6)), possibly through bisintercalation. A cell viability assay was used to demonstrate that both compounds are capable of mediating cytotoxicity at micromolar concentrations in SNB19 brain tumor cells.

  报道了两种新颖的双（r啶）铂（II）配合物的制备。带电荷的4+结合物可能通过双嵌入与双链天然DNA（K（i）> 10（6））强烈结合。细胞活力测定用于证明两种化合物均能在SNB19脑肿瘤细胞中以微摩尔浓度介导细胞毒性。