N1,N4-双-Boc-亚精胺 | 85503-20-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: N1,N4-双-Boc-亚精胺
• 中文别名: N1，N4-双-Boc-亚精胺；N-(4-氨基丁基)-N-[3-[[(1,1-二甲基乙氧基)羰基]氨基]丙基]氨基甲酸1,1-二甲基乙酯
• 英文名称: N,N-bis(tert-butoxycarbonyl)spermidine
• 英文别名: tert-butyl (4-aminobutyl)(3-((tert-butoxycarbonyl)amino)propyl)carbamate；{3-[(4-aminobutyl)-tert-butoxycarbonylamino]propyl}carbamic acid tert-butyl ester；N¹,N⁴-bis-Boc-spermidine；N1,N4-Bis-Boc-spermidine；tert-butyl N-(4-aminobutyl)-N-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]carbamate
• CAS: 85503-20-4
• 化学式: C₁₇H₃₅N₃O₄
• 分子量: 345.483
• InChiKey: GQZZMJDEWJRWRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  93.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 储存条件：
  -20°C，应密封保存，在干燥环境中并充气。

反应信息

• 作为反应物：
  描述：

  N1,N4-双-Boc-亚精胺 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙二醇二甲醚 为溶剂， 反应 2.0h， 生成 3-<(1,1-dimethylethoxycarbonyl)amino>-11-methyl-20-(1,1-dimethylethoxycarbonyl)-12,14-dioxo-2,4,11,15,20,24-hexaazapentacos-2-enedioic acid, bis(1,1-dimethylethyl) ester
  参考文献：
  名称：

  Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 1. Structural Modifications of the Hydroxyglycine Moiety

  摘要：

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent currently commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Using the general concept of bioisosteric replacement, variations of the hydroxyglycine central "C" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. By this way, the malonic derivative 13a was discovered as the first example of a new series of potent immunosuppressive agents encompassing a retro-amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a which proved to be equally active as DSG in our GVHD model. Finally 27a was found to be the most potent derivative, being slightly more active than DSG in a heart allotransplantation model in rats. Due to the absence of chiral center in its structure and to its improved chemical stability compared to DSG, 27a was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm980431g
• 作为产物：
  描述：

  (3-氧代丙基)氨基甲酸叔丁酯 在 palladium on activated charcoal 4 A molecular sieve 、 氢气 、 sodium cyanoborohydride 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 N1,N4-双-Boc-亚精胺
  参考文献：
  名称：

  An Efficient Synthesis of Selectively Functionalized Spermidine

  摘要：

  本文介绍了一种合成选择性保护 Boc、Fmoc 或 Z-亚精胺衍生物的方法。起始精胺，即 N8-苄氧羰基-N 1-叔丁氧羰基精胺，是通过还原胺化反应制备的。

  DOI：

  10.1055/s-1994-25400

文献信息

• Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives
  作者：Elodie Jagu、Rachid Djilali、Sébastien Pomel、Florence Ramiandrasoa、Stéphanie Pethe、Raphaël Labruère、Philippe M. Loiseau、Casimir Blonski

  DOI：10.1016/j.bmcl.2014.11.073

  日期：2015.1

  structure–activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. Among them, a spermidine derivative (compound 13) was specifically active in vitro against Leishmania donovani axenic amastigotes (IC50 at 5.4 μM; Selectivity Index >18.5) and a spermine derivative (compound 28) specifically active against Trypanosoma

  对多胺衍生物的构效关系研究导致了17种化合物的合成和抗运动型活性的测定。其中，亚精胺衍生物（化合物13）在体外对利什曼原虫多虫尼阿米虫（IC 50为5.4μM ；选择性指数> 18.5）具有特异性活性，而亚精胺衍生物（化合物28）对布氏锥虫（Trypanosoma brucei gambiense）具有特异性活性（IC 50对1.9μM;选择性指数> 52）。
• Synthesis and Biological Activity of Anthrapyrazoles Derivatives as Potential Antitumor Agents
  作者：Jianhong Wang、Huijun Zhao、Zhaoyang Luo、Zhaoyi Wang、Yahong Zhang、Jin Zhao

  DOI：10.2174/1573406410666140428152227

  日期：2014.10.23

  We have synthesized a series of anthrapyrazoles derivatives. The biological results indicated that these derivatives exhibited potent in vitro cytotoxicity against different cancer cell lines (human hepatocellular carcinoma HepG2 and BEL-7402, human colonic carcinoma HCT-116 and HT-29) and drug-resistant human hepatoma cell line (SMMC-7721). Among them, the polyamine-based anthrapyrazole derivatives 4c and 4f-g showed superior cytotoxicity than that of Mitoxantrone both on cancer cell lines and the drug-resistant subline. However, the DNA relaxation assay revealed that they had insignificant topoisomerase II inhibition. These results clearly indicate that polyamine side chains will have a profound effect on the cytotoxicity of anthrapyrazoles derivatives.

  我们合成了一系列的蒽吡唑衍生物。生物学结果表明，这些衍生物在不同的癌细胞系（人肝细胞癌HepG2和BEL-7402，人结肠癌HCT-116和HT-29）以及耐药的人肝癌细胞系（SMMC-7721）上表现出强的体外细胞毒性。其中，基于多胺的蒽吡唑衍生物4c和4f-g在癌细胞系和耐药亚系中显示出优于美托沙星的细胞毒性。然而，DNA松弛实验揭示它们对拓扑异构酶II的抑制作用不显著。这些结果清楚地表明，多胺侧链对蒽吡唑衍生物的细胞毒性具有深远的影响。
• Synthesis and in vitro antikinetoplastid activity of polyamine–hydroxybenzotriazole conjugates
  作者：Elodie Jagu、Sébastien Pomel、Alba Diez-Martinez、Florence Ramiandrasoa、R. Luise Krauth-Siegel、Stéphanie Pethe、Casimir Blonski、Raphaël Labruère、Philippe M. Loiseau

  DOI：10.1016/j.bmc.2016.10.013

  日期：2017.1

  however trypanocidal against Trypanosoma brucei gambiense with an IC50 value of 1μM and was completely devoid of cytotoxicity. On the intramacrophage amastigotes of Leishmania donovani, a N2-spermidine conjugate of this series, exhibited an interesting IC50 value of 3μM associated with both low cytotoxicity against axenic Leishmania donovani. These new compounds are promising leads for the development of

  已经合成了十三种与羟基苯并三唑偶联的新的多胺衍生物，并对其体外抗动素体活性进行了评估。锥虫锥虫还原酶（TryR）被认为是潜在的靶标。在所有测试的分子中，只有一种化合物（N3-亚精胺-苯并三唑衍生物）对该酶具有相关的抑制活性，但对寄生虫没有活性。然而，相应的Boc保护的亚精胺-苯并三唑对布氏锥虫有锥虫杀作用，IC50值为1μM，完全没有细胞毒性。在Leishmania donovani的巨噬细胞内无鞭毛体上，该系列的N2-亚精胺结合物表现出令人感兴趣的IC50值为3μM，与对轴突性Leishmania donovani的低细胞毒性有关。
• Design, synthesis and anticancer activity of 2-amidomethoxy-1,4-naphthoquinones and its conjugates with Biotin/polyamine
  作者：Manoj Manickam、Pulla Reddy Boggu、Thanigaimalai Pillaiyar、Yeo Jin Nam、Md. Abdullah、Seung Jin Lee、Jong Seong Kang、Sang-Hun Jung

  DOI：10.1016/j.bmcl.2020.127685

  日期：2021.1

  Among the synthesized compounds, naphthoquinone amines, 5 (0.8; 0.6; 0.8), 14 (0.8; 0.6; 0.5) and the amine precursor, 4 (1.3; 0.3; 1.0) displayed potent anticancer activities. A tumor targeting drug delivery system was achieved by synthesizing the conjugate 6 (1.4; 0.5; 1.1) of naphthoquinone-amine 5 and Biotin which also proved its potency. Finally, to introduce polyamine conjugate, spermidine was attached

  在先前工作的基础上，准备了一系列5-羟基-2-氨基甲氧基-1,4-萘醌，以建立针对三种细胞系的抗癌活性（IC 50以µM为单位）的结构-活性关系研究。colo205（结肠腺癌），T47D（乳腺导管癌）和K562（慢性粒细胞性白血病）。在合成的化合物中，萘醌胺5（0.8; 0.6; 0.8），14（0.8; 0.6; 0.5）和胺前体4（1.3; 0.3; 1.0）具有较强的抗癌活性。通过合成萘醌-胺5的缀合物6（1.4; 0.5; 1.1）实现了肿瘤靶向药物递送系统生物素也证明了其功效。最后，为了引入多胺缀合物，将亚精胺与2-酰胺基甲氧基-1,4-萘醌连接。萘醌-亚精胺缀合物27（1.2； 1.7； 1.7）也保留了活性。因此，探索了有效的萘醌胺，并开发了生物素/聚胺缀合物作为靶向肿瘤的药物递送系统。
• Synthesis and Biological Evaluation of Novel Aromatic Imide-Polyamine Conjugates
  作者：Ming Li、Yuxia Wang、Jianying Zhang、Songqiang Xie、Chaojie Wang、Yingliang Wu

  DOI：10.3390/molecules21121637

  日期：——

  Three types of conjugates in which aromatic imide scaffolds were coupled to diverse amine/polyamine motifs were synthesized, and their antitumor activities were evaluated in vitro and in vivo. Results showed that the conjugate 11e of 1,8-naphthilimide with spermine had pronounced effects on inhibiting tumor cell proliferation and inducing tumor cell apoptosis via ROS-mediated mitochondrial pathway

  合成了三种类型的偶联物，其中芳香酰亚胺支架与不同的胺/多胺基序偶联，并在体外和体内评估了它们的抗肿瘤活性。结果表明，1,8-萘酰亚胺与精胺的偶联物11e通过ROS介导的线粒体途径抑制肿瘤细胞增殖和诱导肿瘤细胞凋亡具有显着作用。对三种 H22 肿瘤移植模型的体内测定表明，化合物 11e 在预防肺癌转移和延长寿命方面发挥了强大的能力。此外，11e在抑制肿瘤生长和改善体重指数方面的功效优于阳性对照，amonafide。我们的研究表明，化合物 11e 是一种有价值的先导化合物，可用于进一步研究。