[3-(3-cyanopropylamino)propyl]carbamic acid tert-butyl ester | 152844-22-9

• 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
• 英文名称: [3-(3-cyanopropylamino)propyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[3-(3-cyanopropylamino)propyl]carbamate
• CAS: 152844-22-9
• 化学式: C₁₂H₂₃N₃O₂
• 分子量: 241.334
• InChiKey: BSJXQZLNRVEILK-UHFFFAOYSA-N

物化性质

• 沸点：
  404.6±30.0 °C(Predicted)
• 密度：
  1.000±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  74.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [3-(3-cyanopropylamino)propyl]carbamic acid tert-butyl ester 在 镍 sodium hydroxide 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 tert-butyl N-[3-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-[4-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]amino]butyl]amino]propyl]carbamate
  参考文献：
  名称：

  Synthese derp-Cumaroylspermidine

  摘要：

  The Synthesis of p‐CumaroylspermidinesThe synthesis of three mono[(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoyl]spermidines, 10, 20, and 28, three bis[(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoyl]spermidines, 6, 16, and 25, and one tris[(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoyl]‐spermidine is described.

  DOI：

  10.1002/hlca.19960790222
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 24.0h， 生成 [3-(3-cyanopropylamino)propyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  炭疽隐性铁载体生物合成的酶促逻辑：AsbA 催化柠檬酸和亚精胺的 ATP 依赖性缩合

  摘要：

  Petrobactin 是一种铁螯合铁载体，最初从 Marinobactercarbonoclastus 中分离出来，已被证明在缺铁条件下的生长和致命的生物恐怖主义剂炭疽芽孢杆菌的毒力中发挥重要作用。最近显示它不与铁钙蛋白结合，使其被指定为可以避开哺乳动物免疫系统的“隐形铁载体”。已知非核糖体肽合成酶 (NRPS) 和不依赖 NRPS 的铁载体 (NIS) 合成酶的独特组合是炭疽芽孢杆菌中石油杆菌素生物合成所必需的。此处显示来自炭疽芽孢杆菌的 AsbA，第一种被生化表征的 A 型 NIS 合成酶，催化柠檬酸与亚精胺的 N8 的 ATP 依赖性区域选择性缩合，但不与 N1-(3,4-二羟基苯甲酰基)-亚精胺.

  DOI：

  10.1021/ja072391o

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）。
• 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。
• New Ianthelliformisamine Derivatives as Antibiotic Enhancers against Resistant Gram-Negative Bacteria
  作者：Cyril Pieri、Diane Borselli、Carole Di Giorgio、Michel De Méo、Jean-Michel Bolla、Nicolas Vidal、Sébastien Combes、Jean Michel Brunel

  DOI：10.1021/jm500194e

  日期：2014.5.22

  A series consisting of ianthelliformisamimes A, B, and C as well as its synthetic analogues was prepared in high chemical yield, from 27 to 91%, using peptide coupling as the key step, and the compounds were evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives against Pseudomonas aeruginosa when combined with doxycycline was precisely evaluated utilizing bioluminescence to measure ATP efflux and fluorescence to evaluate membrane depolarization.
• Design, synthesis and antimalarial/anticancer evaluation of spermidine linked artemisinin conjugates designed to exploit polyamine transporters in Plasmodium falciparum and HL-60 cancer cell lines
  作者：James Chadwick、Michael Jones、Amy E. Mercer、Paul A. Stocks、Stephen A. Ward、B. Kevin Park、Paul M. O’Neill

  DOI：10.1016/j.bmc.2010.02.035

  日期：2010.4

  A series of artemisinin-spermidine conjugates designed to utilise the upregulated polyamine transporter found in cancer cells have been prepared. These conjugates were evaluated against human promyelocytic leukaemia HL-60 cells and chloroquine-sensitive 3D7 Plasmodium falciparum and several show promising anticancer and antimalarial activity. Although some limitations in this vector-based approach are apparent, a number of high potency Boc-protected analogues were identified with activity against malaria parasites as low as 0.21 nM. (C) 2010 Elsevier Ltd. All rights reserved.
• Polyaminoquinoline Iron Chelators for Vectorization of Antiproliferative Agents: Design, Synthesis, and Validation
  作者：Vincent Corcé、Emmanuelle Morin、Solène Guihéneuf、Eric Renault、Stéphanie Renaud、Isabelle Cannie、Raphaël Tripier、Luís M. P. Lima、Karine Julienne、Sébastien G. Gouin、Olivier Loréal、David Deniaud、François Gaboriau

  DOI：10.1021/bc300324c

  日期：2012.9.19

  Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 mu M. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.