[4-(3,5-bis(4-[tert-butoxycarbonyl-(4-tert-butoxycarbonylaminobutyl)amino]butylcarbamoyl)-benzoylamino)butyl](4-tert-butoxycarbonylaminobutyl)-carbamic acid tert-butyl ester | 1258531-67-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-(3,5-bis(4-[tert-butoxycarbonyl-(4-tert-butoxycarbonylaminobutyl)amino]butylcarbamoyl)-benzoylamino)butyl](4-tert-butoxycarbonylaminobutyl)-carbamic acid tert-butyl ester
• 英文别名: [4-(3,5-Bis-{4-[tert-butoxycarbonyl-(4-tert-butoxycarbonylamino-butyl)-amino]-butylcarbamoyl}-benzoylamino)-butyl]-(4-tert-butoxycarbonylamino-butyl)-carbamic acid tert-butyl ester；tert-butyl N-[4-[[3,5-bis[4-[(2-methylpropan-2-yl)oxycarbonyl-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]amino]butylcarbamoyl]benzoyl]amino]butyl]-N-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]carbamate
• CAS: 1258531-67-7
• 化学式: C₆₃H₁₁₁N₉O₁₅
• 分子量: 1234.63
• InChiKey: NFSVGSSHRUJDAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  87
• 可旋转键数：
  45
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  291
• 氢给体数：
  6
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  [4-(3,5-bis(4-[tert-butoxycarbonyl-(4-tert-butoxycarbonylaminobutyl)amino]butylcarbamoyl)-benzoylamino)butyl](4-tert-butoxycarbonylaminobutyl)-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 4.33h， 以99%的产率得到N¹,N³,N⁵-tris(4-((4-aminobutyl)amino)butyl)benzene-1,3,5-tricarboxamide hexahydrochloride
  参考文献：
  名称：

  [EN] POLYAMINE TRANSPORT INHIBITORS AS NOVEL THERAPEUTICS
  [FR] INHIBITEURS DU TRANSPORT DE LA POLYAMINE EN TANT QUE NOUVELLE THÉRAPEUTIQUE

  摘要：

  公开号：

  WO2010148390A3
• 作为产物：
  描述：

  1,3,5-苯三甲酰氯 、 tert-butyl (4-aminobutyl)(4-((tert-butoxycarbonyl)amino)butyl)carbamate 在 potassium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 以78%的产率得到[4-(3,5-bis(4-[tert-butoxycarbonyl-(4-tert-butoxycarbonylaminobutyl)amino]butylcarbamoyl)-benzoylamino)butyl](4-tert-butoxycarbonylaminobutyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] POLYAMINE TRANSPORT INHIBITORS AS NOVEL THERAPEUTICS
  [FR] INHIBITEURS DU TRANSPORT DE LA POLYAMINE EN TANT QUE NOUVELLE THÉRAPEUTIQUE

  摘要：

  公开号：

  WO2010148390A3

文献信息

• POLYAMINE TRANSPORT INHIBITORS AS NOVEL THERAPEUTICS
  申请人：Phanstiel Otto

  公开号：US20120172449A1

  公开（公告）日：2012-07-05

  Novel polyamine transport inhibitors have been synthesized and demonstrated to block the uptake of native polyamines into human cancer cells. A combination therapy of the transport inhibitor and DFMO (a drug which blocks polyamine biosynthesis) provided synergistic activity against a metastatic human colon cancer cell line. The strategy uses polyamine depletion and polyamine metabolism to generate reactive oxygen species within cells as a novel way to treat cancers. This approach may be implemented for widespread use in the treatment of diseases which rely upon polyamine transport activity for proliferation.

  新型聚胺运输抑制剂已经合成并证明可以阻止天然聚胺进入人类癌细胞。运输抑制剂和DFMO（一种阻止聚胺生物合成的药物）的联合治疗对转移性人类结肠癌细胞系表现出协同作用。该策略利用聚胺耗竭和聚胺代谢在细胞内产生活性氧自由基的新方法来治疗癌症。这种方法可以在依赖聚胺运输活性进行增殖的疾病的广泛治疗中实施。
• [EN] POLYAMINE TRANSPORT INHIBITORS AS NOVEL THERAPEUTICS<br/>[FR] INHIBITEURS DU TRANSPORT DE LA POLYAMINE EN TANT QUE NOUVELLE THÉRAPEUTIQUE
  申请人：UNIV CENTRAL FLORIDA RES FOUND

  公开号：WO2010148390A3

  公开（公告）日：2011-04-21
• US9212131B2
  申请人：——

  公开号：US9212131B2

  公开（公告）日：2015-12-15
• US9730902B2
  申请人：——

  公开号：US9730902B2

  公开（公告）日：2017-08-15
• 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.