(4-tert-butoxycarbonylaminobutyl)-{4-[tert-butoxycarbonyl-(3-cyanopropyl)amino]butyl}carbamic acid tert-butyl ester | 926652-67-7

• 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: (4-tert-butoxycarbonylaminobutyl)-{4-[tert-butoxycarbonyl-(3-cyanopropyl)amino]butyl}carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-(3-cyanopropyl)-N-[4-[(2-methylpropan-2-yl)oxycarbonyl-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]amino]butyl]carbamate
• CAS: 926652-67-7
• 化学式: C₂₇H₅₀N₄O₆
• 分子量: 526.717
• InChiKey: HFFWFSQEHGHHIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  37
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4-tert-butoxycarbonylaminobutyl)-{4-[tert-butoxycarbonyl-(3-cyanopropyl)amino]butyl}carbamic acid tert-butyl ester 在 镍 ammonium hydroxide 、 sodium tetrahydroborate 、 氨 、 氢气 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 24.0h， 生成 tert-butyl N-[4-[[3,4-bis[(Z)-octadec-9-enoxy]phenyl]methylamino]butyl]-N-[4-[(2-methylpropan-2-yl)oxycarbonyl-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]amino]butyl]carbamate
  参考文献：
  名称：

  Synthesis and Transfection Efficiencies of New Lipophilic Polyamines

  摘要：

  A homologous series of lipophilic polyamines was synthesized and evaluated for DNA delivery and transfection efficiency. The series contained 1,4-butanediamine, 1,8-octanediamine, 2-[2-(2-amino-ethoxy)-ethoxy]-ethylamine, homospermidine, and homospermine covalently attached via their N-1 terminus to a 3,4-bis(oleyloxy)-benzyl motif. In addition, homospermidine and homospermine were also attached via amide linkers. The homospermidine derivatives (i.e., benzyl tether 25 and benzamide tether 27) showed a 3-fold and 4-fold respective enhancement in delivery of AlexaFluor-488-labeled DNA over the butanediamine analogue 22. Homospermine derivative 26 was shown to inhibit C-14-spermine uptake (IC50 similar to 10 mu M), which implied that 26 is able to compete effectively for polyamine recognition sites on the cell surface. This study demonstrated that the number and position of the positive charges along the polyamine scaffold plays a key role in DNA delivery and in determining the transfection efficiency.

  DOI：

  10.1021/jm0607101
• 作为产物：
  描述：

  tert-butyl (4-aminobutyl)(4-((tert-butoxycarbonyl)amino)butyl)carbamate 在 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 32.0h， 生成 (4-tert-butoxycarbonylaminobutyl)-{4-[tert-butoxycarbonyl-(3-cyanopropyl)amino]butyl}carbamic acid tert-butyl ester
  参考文献：
  名称：

  Polyaminoquinoline Iron Chelators for Vectorization of Antiproliferative Agents: Design, Synthesis, and Validation

  摘要：

  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.

  DOI：

  10.1021/bc300324c

文献信息

• Designing the Polyamine Pharmacophore: Influence of <i>N</i>-Substituents on the Transport Behavior of Polyamine Conjugates
  作者：Navneet Kaur、Jean-Guy Delcros、Jennifer Archer、Nathan Z. Weagraff、Bénédicte Martin、Otto Phanstiel IV

  DOI：10.1021/jm701341k

  日期：2008.4.1

  were able to retain their PAT selectivity and cytotoxicity properties in the presence or absence of AG. In contrast, the lead compound 1b (containing a terminal NH 2 group) revealed a dramatic reduction in both its PAT-targeting ability and cytotoxicity in the absence of AG. An improved balance between these three properties of PAT-targeting, cytotoxicity and metabolic stability can be attained via N-methylation

  合成了N-乙氧基化的N-芳基甲基多胺共轭物，并评估了它们靶向多胺转运蛋白（PAT）的能力。为了了解N-乙基化对PAT选择性的影响，将乙基附加到PAT选择性N（1）-蒽基甲基高嘧啶衍生物1b上。在L1210鼠白血病细胞和两种中国仓鼠卵巢细胞系（PAT活性CHO和PAT缺陷的CHO-MG）中的生物评价显示，药效基团1b的N（1）或N（5）乙基化后，PAT靶向能力急剧下降。使用胺氧化酶抑制剂氨基胍（AG，2 mM）进行的实验表明，在存在或不存在AG的情况下，N（9）-乙基和N（9）-甲基类似物都能保留其PAT选择性和细胞毒性。相比之下，在没有AG的情况下，先导化合物1b（包含一个末端NH 2基团）显示出PAT靶向能力和细胞毒性都大大降低了。通过在N（9）位置进行N-甲基化，可以在靶向PAT的这三个特性，细胞毒性和代谢稳定性之间达到更好的平衡。
• US7910363B1
  申请人：——

  公开号：US7910363B1

  公开（公告）日：2011-03-22
• 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.
• Synthesis and Transfection Efficiencies of New Lipophilic Polyamines
  作者：Richard Andrew Gardner、Mattias Belting、Katrin Svensson、Phanstiel

  DOI：10.1021/jm0607101

  日期：2007.1.1

  A homologous series of lipophilic polyamines was synthesized and evaluated for DNA delivery and transfection efficiency. The series contained 1,4-butanediamine, 1,8-octanediamine, 2-[2-(2-amino-ethoxy)-ethoxy]-ethylamine, homospermidine, and homospermine covalently attached via their N-1 terminus to a 3,4-bis(oleyloxy)-benzyl motif. In addition, homospermidine and homospermine were also attached via amide linkers. The homospermidine derivatives (i.e., benzyl tether 25 and benzamide tether 27) showed a 3-fold and 4-fold respective enhancement in delivery of AlexaFluor-488-labeled DNA over the butanediamine analogue 22. Homospermine derivative 26 was shown to inhibit C-14-spermine uptake (IC50 similar to 10 mu M), which implied that 26 is able to compete effectively for polyamine recognition sites on the cell surface. This study demonstrated that the number and position of the positive charges along the polyamine scaffold plays a key role in DNA delivery and in determining the transfection efficiency.