tert-butyl (4-((4-aminobutyl)(tert-butoxycarbonyl)amino)-butyl)(methyl)carbamate | 1446751-81-0

• 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: tert-butyl (4-((4-aminobutyl)(tert-butoxycarbonyl)amino)-butyl)(methyl)carbamate
• 英文别名: tert-butyl N-(4-aminobutyl)-N-[4-(tert-butoxycarbonylmethylamino)butyl]carbamate；tert-butyl (4-((4-aminobutyl)(tert-butoxycarbonyl)amino)butyl)(methyl)carbamate；tert-Butyl (4-((4-aminobutyl)(tert-butoxycarbonyl)amino)butyl)(methyl)carbamate；tert-butyl N-(4-aminobutyl)-N-[4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butyl]carbamate
• CAS: 1446751-81-0
• 化学式: C₁₉H₃₉N₃O₄
• 分子量: 373.536
• InChiKey: COLDHTINTQUKRY-UHFFFAOYSA-N

物化性质

• 沸点：
  465.8±34.0 °C(predicted)
• 密度：
  1.016±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  85.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-((4-aminobutyl)(tert-butoxycarbonyl)amino)-butyl)(methyl)carbamate 在 sodium tetrahydroborate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 N¹,N¹′-[1,4-phenylenebis(methylene)]bis{N⁴-[4-(methylamino)butyl]butane-1,4-diamine}
  参考文献：
  名称：

  Development of Polyamine Transport Ligands with Improved Metabolic Stability and Selectivity against Specific Human Cancers

  摘要：

  Polyamine homeostasis is critical for life and is accomplished via a balance of polyamine biosynthesis, degradation, and transport. Rapidly dividing cancer cells have been shown to have high polyamine transport activity compared to normal cells, likely due to their high requirement for polyamine metabolites. The polyamine transport system (PTS) is a therapeutically relevant target, as it can provide selective drug delivery to cancer cells. This report describes the synthesis and biological evaluation of multimeric polyamine derivatives as efficient PTS ligands. Arylmethyl-polyamine derivatives were synthesized to address two important concerns in PTS drug design: (a) PTS selectivity and (b) stability to amine oxidases. N-1,N-1'-[Naphthalene-1,4-diylbis(methylene)]bis{N-4-[4-(methylamino)butyl])-butane-1,4-diamine}, 3b, was found to have an optimal balance between these parameters and demonstrated excellent targeting of melanoma (e.g., MALME-3M) and breast cancer cells (e.g., T47D) over other cancer cell lines. These results provide a method to selectively target cancers via their intrinsic need for polyamine metabolites.

  DOI：

  10.1021/jm400496a
• 作为产物：
  描述：

  methanesulfonic acid 4-(tert-butoxycarbonyl-methyl-amino)-butyl ester 在 potassium carbonate 、 水杨醛 、 sodium sulfate 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 3.83h， 生成 tert-butyl (4-((4-aminobutyl)(tert-butoxycarbonyl)amino)-butyl)(methyl)carbamate
  参考文献：
  名称：

  [EN] POLYAMINE TRANSPORT SELECTIVE THERAPEUTIC AGENTS WITH ENHANCED STABILITY
  [FR] AGENTS THÉRAPEUTIQUES SÉLECTIFS EN TERMES DE TRANSPORT DES POLYAMINES À STABILITÉ PLUS ÉLEVÉE

  摘要：

  本文披露了二取代芳基多胺化合物及其制备和使用方法。这些二取代多胺化合物作为PTS靶向剂，能够有选择性地靶向多胺转运系统（PTS），具有高效性，并且在胺氧化酶存在的情况下具有改善的稳定性。

  公开号：

  WO2013148230A1

文献信息

• POLYAMINE TRANSPORT SELECTIVE THERAPEUTIC AGENTS WITH ENHANCED STABILITY
  申请人：UNIVERSITY OF CENTRAL FLORIDA RESEARCH FOUNDATION. INC.

  公开号：US20150017231A1

  公开（公告）日：2015-01-15

  Disclosed herein are di-substituted aryl polyamine compounds and methods of making and using the same. The di-substituted polyamine compounds act as PTS targeting agents, which selectively target the polyamine transport system (PTS) with high efficacy and have improved stability in the presence of amine oxidases.

  本文公开了二取代芳基多胺化合物及其制备和使用方法。这些二取代多胺化合物作为PTS定向剂，能够高效地选择性地靶向多胺转运系统(PTS)，并且在存在胺氧化酶的情况下具有改善的稳定性。
• Polyamine transport selective therapeutic agents with enhanced stability
  申请人：Phanstiel, IV Otto

  公开号：US09346741B2

  公开（公告）日：2016-05-24

  Disclosed herein are di-substituted aryl polyamine compounds and methods of making and using the same. The di-substituted polyamine compounds act as PTS targeting agents, which selectively target the polyamine transport system (PTS) with high efficacy and have improved stability in the presence of amine oxidases.

  本文披露了双取代芳基多胺化合物的方法和制备方法。这些双取代多胺化合物作为PTS靶向剂，能够高效地选择性地靶向多胺转运系统（PTS），并在胺氧化酶存在的情况下具有改善的稳定性。
• Polyamine Transport Inhibitors: Design, Synthesis, and Combination Therapies with Difluoromethylornithine
  作者：Aaron Muth、Meenu Madan、Jennifer Julian Archer、Nicolette Ocampo、Luis Rodriguez、Otto Phanstiel

  DOI：10.1021/jm401174a

  日期：2014.1.23

  The development of polyamine transport inhibitors (PTIs), in combination with the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), provides a method to target cancers with high polyamine requirements. The DFMO+PTI combination therapy results in sustained intracellular polyamine depletion and cell death. A series of substituted benzene derivatives were evaluated for their ability to inhibit the import of spermidine in DFMO-treated Chinese hamster ovary (CHO) and L3.6pl human pancreatic cancer cells. Several design features were discovered which strongly influenced PTI potency, sensitivity to amine oxidases, and cytotoxicity. These included changes in (a) the number of polyamine chains appended to the ring system, (b) the polyamine sequence, (c) the attachment linkage of the polyamine to the aryl core, and (d) the presence of a terminal N-methyl group. Of the series tested, the optimal design was N-1,N-1',N-1 ''-(benzene-1,3,5-triyltris(methylene))tris(N-4-(4-(methylamino)butyl)butane-1,4-diamine, 6b, which contained three N-methylhomospermidine motifs. This PTI exhibited decreased sensitivity to amine oxidases and low toxicity as well as high potency (EC50 = 1.4 mu M) in inhibiting the uptake of spermidine (1 mu M) in DFMO-treated L3.6pl human pancreatic cancer cells.
• US9346741B2
  申请人：——

  公开号：US9346741B2

  公开（公告）日：2016-05-24
• US9926260B2
  申请人：——

  公开号：US9926260B2

  公开（公告）日：2018-03-27