3-[3-[2-[Bis[3-[bis(2-cyanoethyl)amino]propyl]amino]ethyl-[3-[bis(2-cyanoethyl)amino]propyl]amino]propyl-(2-cyanoethyl)amino]propanenitrile | 66169-74-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-[3-[2-[Bis[3-[bis(2-cyanoethyl)amino]propyl]amino]ethyl-[3-[bis(2-cyanoethyl)amino]propyl]amino]propyl-(2-cyanoethyl)amino]propanenitrile
• CAS: 66169-74-2
• 化学式: C₃₈H₆₀N₁₄
• 分子量: 712.988
• InChiKey: QNAPKFAJIICQNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  52
• 可旋转键数：
  35
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  210
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  3-[3-[2-[Bis[3-[bis(2-cyanoethyl)amino]propyl]amino]ethyl-[3-[bis(2-cyanoethyl)amino]propyl]amino]propyl-(2-cyanoethyl)amino]propanenitrile 在 氢气 、 镍 作用下， 生成 N¹-(3-Amino-propyl)-N¹-(3-{{3-[bis-(3-amino-propyl)-amino]-propyl}-[2-(bis-{3-[bis-(3-amino-propyl)-amino]-propyl}-amino)-ethyl]-amino}-propyl)-propane-1,3-diamine
  参考文献：
  名称：

  Surface Engineered Dendrimers as Antiangiogenic Agent and Carrier for Anticancer Drug: Dual Attack on Cancer

  摘要：

  本研究工作描述了模拟内源性血管生成抑制剂内皮抑素表面结构的精氨酸偶联3.0G聚(丙烯)亚胺(PPI)树枝状大分子的制备，用于肿瘤特异性传递模型抗癌药物盐酸多柔比星(Dox)。通过FTIR、NMR、TEM和质谱法确认了PPI树枝状大分子的合成以及精氨酸与表面基团的 conjugation。通过平衡透析方法加载药物，并评估所开发的制剂的包封效率、溶血毒性、体外药物释放、稳定性、通过体内鸡胚绒毛尿囊膜(CAM)试验评估的抗血管生成活性，以及使用MCF-7癌细胞系进行的抗癌活性和细胞摄取。该系统表现出初始的快速释放随后持续释放Dox，并在CAM试验中显示出显著的抗血管生成活性。此外，精氨酸偶联的树枝状大分子在体内研究中被发现能抑制MCF-7细胞系的癌细胞生长。细胞摄取研究表明，与自由药物相比，制剂更优先被肿瘤细胞摄取。因此，针对癌细胞组织的两种攻击方式，即抑制血管生成和通过抗癌药物杀灭癌细胞，可能成为治疗致命疾病癌症的有前景的方法。

  DOI：

  10.1166/jnn.2014.8677
• 作为产物：
  描述：

  3,3',3'',3'''-(乙烯二次氮基)四丙腈 在 溶剂黄146 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 36.0h， 生成 3-[3-[2-[Bis[3-[bis(2-cyanoethyl)amino]propyl]amino]ethyl-[3-[bis(2-cyanoethyl)amino]propyl]amino]propyl-(2-cyanoethyl)amino]propanenitrile
  参考文献：
  名称：

  Anionic sulfonated and carboxylated PPI dendrimers with the EDA core: synthesis and characterization of selective metal complexing agents

  摘要：

  本文中，我们描述了具有乙二胺（EDA）核心的新型磺酸化和羧酸化的聚（丙烯亚胺）（PPI）树枝状大分子的合成与表征，涉及1代、2代和3代。通过使用Cu$^{2+}$作为探针的UV-Vis和EPR光谱学手段，我们得出结论，这些树枝状大分子在金属离子的配位上显示出特定的模式。与UV-Vis研究一致，羧酸化化合物的EPR光谱由3种不同信号组成，这些信号随着铜浓度的增加出现并随后消失，对应于不同铜配位位点的饱和。在铜浓度最低至1:1的Cu$^{2+}$与树枝状大分子摩尔比时，光谱特征为树枝状大分子核心的CuN2O2配位。在较高Cu$^{2+}$浓度下出现的光谱表明，离子在外周位置配位，以四边形平面几何结构在一个氮和三个氧原子进行配位，处于受限运动条件。对于所测试的最高浓度，铜离子被限制在树枝状大分子的外表面，具有CuO4配位。对于磺酸盐系统，EPR结果表明，与氮位点的Cu$^{2+}$相互作用较弱，与氧（SO3$^-$）位点的相互作用较强，相较于通过EPR测量的羧酸盐系统的相互作用。

  DOI：

  10.1039/c3dt32870h

文献信息

• NOVEL NITRILE AND AMIDOXIME COMPOUNDS AND METHODS OF PREPARATION
  申请人：Lee Wai Mun

  公开号：US20090111965A1

  公开（公告）日：2009-04-30

  The present application relates to semiconductor processing compositions comprising at least one compound containing at least one amidoxime functional group and to methods of using these compositions in semiconductor processing. The present application also describes the preparation of amidoximes for a semiconductor processing composition by (a) mixing a cyanoethylation catalyst, a nucleophile and an alpha-unsaturated nitrile to produce a cyanoethylation product; and (b) converting a cyano group in the cyanoethylation product into an amidoxime functional group.

  本申请涉及包含至少一个含有至少一个酰胺肟功能团的化合物的半导体加工组合物，以及使用这些组合物进行半导体加工的方法。本申请还描述了通过(a)混合氰乙基化催化剂、亲核试剂和不饱和α腈以产生氰乙基化产品；(b)将氰乙基化产品中的氰基团转化为酰胺肟功能团来制备用于半导体加工组合物的酰胺肟的方法。
• Surface Engineered Dendrimers as Antiangiogenic Agent and Carrier for Anticancer Drug: Dual Attack on Cancer
  作者：K. Jain、N. K. Jain

  DOI：10.1166/jnn.2014.8677

  日期：2014.7.1

  The present research work describes the formulation of arginine conjugated 3.0G Poly(propylene) imine (PPI) dendrimers, mimicking the surface structure of an endogenous angiogenesis-inhibitor endostatin; for tumor specific delivery of a model anticancer drug, doxorubicin hydrochloride (Dox). Synthesis of PPI dendrimers and conjugation of arginine to surface groups was confirmed by FTIR, NMR, TEM and mass spectrometry. Drug was loaded by equilibrium dialysis method and developed formulation was evaluated for entrapment efficiency, hemolytic toxicity, in vitro drug release, stability, anti-angiogenic activity via in vivo chick embryo chorioallantoic membrane (CAM) assay, and anticancer activity and cell uptake using MCF-7 cancer cell lines. The system exhibited the initial rapid release followed by sustained release of Dox with significant antiangiogenic activity in the CAM assay. Further, the arginine conjugated dendrimers was found to inhibit growth of cancer cells in ex vivo studies with MCF-7 cell lines. Cell uptake studies suggested that in comparison to free drug the formulation was preferably taken up by the tumor cells. Thus the two pronged attack on cancerous tissue i.e., inhibition of angiogenesis and killing of cancer cells by anticancer drug, might prove to be a promising approach in the treatment of fatal disease, cancer.

  本研究工作描述了模拟内源性血管生成抑制剂内皮抑素表面结构的精氨酸偶联3.0G聚(丙烯)亚胺(PPI)树枝状大分子的制备，用于肿瘤特异性传递模型抗癌药物盐酸多柔比星(Dox)。通过FTIR、NMR、TEM和质谱法确认了PPI树枝状大分子的合成以及精氨酸与表面基团的 conjugation。通过平衡透析方法加载药物，并评估所开发的制剂的包封效率、溶血毒性、体外药物释放、稳定性、通过体内鸡胚绒毛尿囊膜(CAM)试验评估的抗血管生成活性，以及使用MCF-7癌细胞系进行的抗癌活性和细胞摄取。该系统表现出初始的快速释放随后持续释放Dox，并在CAM试验中显示出显著的抗血管生成活性。此外，精氨酸偶联的树枝状大分子在体内研究中被发现能抑制MCF-7细胞系的癌细胞生长。细胞摄取研究表明，与自由药物相比，制剂更优先被肿瘤细胞摄取。因此，针对癌细胞组织的两种攻击方式，即抑制血管生成和通过抗癌药物杀灭癌细胞，可能成为治疗致命疾病癌症的有前景的方法。
• Anionic sulfonated and carboxylated PPI dendrimers with the EDA core: synthesis and characterization of selective metal complexing agents
  作者：Sandra García-Gallego、Michela Cangiotti、Luigi Fiorani、Alberto Fattori、Ma Ángeles Muñoz-Fernández、Rafael Gomez、M. Francesca Ottaviani、F. Javier de la Mata

  DOI：10.1039/c3dt32870h

  日期：——

  Herein we describe the synthesis and characterization of new sulfonated and carboxylated poly(propyleneimino) (PPI) dendrimers with the ethylenediamino (EDA) core, at generations 1, 2 and 3. By means of UV-Vis and EPR spectroscopy, using Cu2+ as a probe, we concluded that these dendrimers show a specific pattern in the coordination of metal ions. In agreement with the UV-Vis studies, EPR spectra of carboxylated compounds are constituted by 3 different signals which appear and then disappear with increasing copper concentration, corresponding to the saturation of different copper complexation sites. At the lowest copper concentration up to a 1 : 1 molar ratio between CuII and the dendrimer, the spectrum is characteristic of a CuN2O2 coordination at the core of the dendrimer. The spectrum appearing at higher CuII concentrations indicates a peripheral location of the ions coordinating one nitrogen and 3 oxygen atoms in a square planar geometry in restricted mobility conditions. For the highest concentrations tested, copper ions are confined at the external dendrimer surface with CuO4 coordination. For sulfonate systems, the EPR results are in line with a weaker interaction of CuII with the nitrogen sites and a stronger interaction with the oxygen (SO3−) groups with respect to the interactions measured by EPR for carboxylate systems.

  本文中，我们描述了具有乙二胺（EDA）核心的新型磺酸化和羧酸化的聚（丙烯亚胺）（PPI）树枝状大分子的合成与表征，涉及1代、2代和3代。通过使用Cu$^2+}$作为探针的UV-Vis和EPR光谱学手段，我们得出结论，这些树枝状大分子在金属离子的配位上显示出特定的模式。与UV-Vis研究一致，羧酸化化合物的EPR光谱由3种不同信号组成，这些信号随着铜浓度的增加出现并随后消失，对应于不同铜配位位点的饱和。在铜浓度最低至1:1的Cu$^2+}$与树枝状大分子摩尔比时，光谱特征为树枝状大分子核心的CuN2O2配位。在较高Cu$^2+}$浓度下出现的光谱表明，离子在外周位置配位，以四边形平面几何结构在一个氮和三个氧原子进行配位，处于受限运动条件。对于所测试的最高浓度，铜离子被限制在树枝状大分子的外表面，具有CuO4配位。对于磺酸盐系统，EPR结果表明，与氮位点的Cu$^2+}$相互作用较弱，与氧（SO3$^-$）位点的相互作用较强，相较于通过EPR测量的羧酸盐系统的相互作用。
• Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development and<i>In Vitro</i>and<i>In Vivo</i>Evaluation
  作者：Keerti Jain、Ashwni Kumar Verma、Prabhat Ranjan Mishra、Narendra Kumar Jain

  DOI：10.1128/aac.04213-14

  日期：2015.5

  The present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR),¹H nuclear magnetic resonance (¹H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency,in vitrodrug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellularLeishmania donovaniamastigotes,in vivopharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagicL. donovaniamastigotes. In thein vitrocell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs.In vivostudies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.

  摘要本研究旨在为两性霉素 B（AmB）开发一种优化的树枝状给药系统。研究人员合成了第五代（5.0G）聚丙烯亚胺（PPI）树枝状聚合物，并与甘露糖共轭，利用傅立叶变换红外光谱（FTIR）、1H 核磁共振（1H-NMR）光谱分析和原子力显微镜（AFM）等多种分析技术对其进行了表征。将甘露糖共轭的 5.0G PPI（MPPI）树枝状聚合物载入 AmB，并评估了药物载入效率、体外药物释放曲线、稳定性、对人红细胞的溶血性毒性、对 J774A.1 巨噬细胞的细胞毒性和细胞摄取量、抗寄生虫性和抗药性。巨噬细胞的细胞毒性、对细胞内利什曼原虫的抗寄生活性、体内药代动力学和生物分布曲线、药物定位指数、毒性和抗利什曼活性。原子力显微镜（AFM）显示，MPPI 树枝状聚合物的尺寸为纳米级，结构接近球状。该共轭物对 AmB 有很好的吸附效率，同时还具有对 pH 值敏感的药物释放特性。在不影响 AmB 的抗寄生虫活性的情况下，它对人类红细胞和巨噬细胞的毒性大大降低。AmB 的树枝状聚合物制剂显示，AmB 对巨噬细胞内唐氏原虫的杀寄生虫活性显著增强。在玻璃细胞摄取研究中，该制剂显示出对巨噬细胞的选择性，具有显著的细胞内摄取作用。进一步的药代动力学和器官分布研究阐明了该制剂的控制给药行为。活体研究表明，MPPIA 具有生物相容性，即使剂量较大，毒性也可忽略不计，而且具有良好的抗利什曼病活性。从这些结果中，我们得出结论，表面工程树枝状聚合物可作为 AmB 的优化递送载体，具有更高的活性和低毒性或可忽略不计的毒性。
• PEGylated PPI dendritic architectures for sustained delivery of H2 receptor antagonist
  作者：Virendra Gajbhiye、P. Vijayaraj Kumar、Rakesh Kumar Tekade、N.K. Jain

  DOI：10.1016/j.ejmech.2008.06.012

  日期：2009.3

  The present study was aimed at synthesizing and exploring the use of long circulating biocompatible PEGylated PPI 5.0G dendrimers for sustained delivery of a H-2 receptor antagonist, Famotidine. PPI 5.0G dendrimers were synthesized and PEGylated using dicarboxylic acid PEG 2000. PEGylation was confirmed by SEC, IR, NMR and MASS spectroscopies. Famotidine was loaded in PFGylated dendritic system and confirmed by IR and differential scanning calorimetry. The PEGylated dendritic system has shown an increased drug loading capacity, a reduced hemolytic toxicity and demonstrated a suitability of PEGylated PPI 5.0G dendrimer for prolonged delivery of Famotidine during in vitro release, in vivo blood level and tissue distribution studies in albino rats. The ulcer index after 5 h of treatment with different formulations was found to be 4.5 +/- 0.28 in case of plain Famotidine solution, while ulcer index was significantly reduced to 0.5 +/- 0.13 in case of Famotidine loaded PEGylated PPI 5.0G dendrimers, indicating sustained release of the drug from drug-PEGylated dendrimer complex. The results suggested that such PEGylated dendrimeric systems could serve as nanoparticulate depot for drugs in body. (C) 2008 Published by Elsevier Masson SAS.