[PtCl(en)(NCEt)]Cl | 1092549-91-1

• 英文名称: [PtCl(en)(NCEt)]Cl
• CAS: 1092549-91-1
• 化学式: C₅H₁₃ClN₃Pt*Cl
• 分子量: 381.164
• InChiKey: MEUZXJWQFQUYPF-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为反应物：
  描述：

  [PtCl(en)(NCEt)]Cl 在 silver nitrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  [EN] PLATINUM ACRIDINE ANTI-CANCER COMPOUNDS AND METHODS THEREOF
  [FR] COMPOSÉS ANTICANCÉREUX À BASE DE PLATINE ET D'ACRIDINE ET PROCÉDÉS POUR LES UTILISER

  摘要：

  揭示了含有铂的吖啶类化合物，对癌症的疗效优于其他铂类化合物。

  公开号：

  WO2010048499A1
• 作为产物：
  描述：

  乙二胺氯化铂(II) 、 丙腈 在 盐酸 作用下， 以 水 为溶剂， 反应 0.2h， 以90%的产率得到[PtCl(en)(NCEt)]Cl
  参考文献：
  名称：

  [EN] TARGETED DELIVERY AND PRODRUG DESIGNS FOR PLATINUM-ACRIDINE ANTI-CANCER COMPOUNDS AND METHODS THEREOF
  [FR] ADMINISTRATION CIBLÉE ET CONCEPTIONS DE PROMÉDICAMENTS POUR COMPOSÉS ANTICANCÉREUX À BASE DE PLATINE ET D'ACRIDINE ET MÉTHODES ASSOCIÉES

  摘要：

  含有环丙啶结构的吖啶类化合物已被披露，显示出比其他顺铂类化合物更有效地对抗癌症。使用一种或多种氨基酸、一种或多种糖、一种或多种聚合醚、C i^aikylene-phenyl-NH-C(0)-R.15、叶酸、av03整合RGD结合肽、他莫昔芬、恩多西芬、表皮生长因子受体、抗体结合物、激酶抑制剂、二唑类化合物、三唑类化合物、噁唑类化合物、厄洛替尼和/或它们的混合物将这些更有效的吖啶类化合物传递到癌细胞核中的方法被披露；其中R]§是一个肽。

  公开号：

  WO2013033430A1

文献信息

• Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models
  作者：Anthony T. S. Lo、Nicole S. Bryce、Alice V. Klein、Mathew H. Todd、Trevor W. Hambley

  DOI：10.1007/s00775-020-01847-3

  日期：2021.5

  5-Aminoalkylamine substituted anthraquinones (AAQs, 1C3 and 1,5C3) were peptide coupled to 1-, 2-, and 3-pyrrole lexitropsins to generate compounds that incorporated both DNA minor groove and intercalating moieties. The corresponding platinum(II) amidine complexes were synthesized through a synthetically facile amine-to-platinum mediated nitrile ‘Click’ reaction. The precursors as well as the corresponding platinum(II)

  1- 和 1,5- 氨基烷基胺取代的蒽醌（AAQ、1C3 和 1,5C3）与 1-、2- 和 3-吡咯 lexitropsins 进行肽偶联，生成掺入 DNA 小沟和嵌入部分的化合物。通过合成简便的胺-铂介导的腈“点击”反应合成了相应的铂(II)脒络合物。在 2D 单层细胞和 3D 肿瘤细胞模型中对前体以及相应的铂 (II) 配合物进行了生物学评估。尽管铂复合物的细胞累积水平比顺铂低五倍，但其细胞毒性仅低三倍。具有两个或三个吡咯基团的复合物的累积量最低，但后者是复合物中活性最高的，超过了 MDA-MB-231 细胞系中顺铂的活性。所有化合物均表现出中等至良好的 DLD-1 细胞球体渗透性，其分布与球体缺乏营养物区域中含吡咯复合物的主动吸收一致。  图文摘要
• 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。
• 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.
• 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.