(4-tert-butoxycarbonylaminobutyl)(4-hydroxybutyl)carbamic acid tert-butyl ester | 805229-97-4

• 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
• 英文名称: (4-tert-butoxycarbonylaminobutyl)(4-hydroxybutyl)carbamic acid tert-butyl ester
• 英文别名: (4-t-Butoxycarbonylaminobutyl)-(4-hydroxybutyl)carbamic acid t-butyl ester；tert-butyl N-(4-hydroxybutyl)-N-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]carbamate
• CAS: 805229-97-4
• 化学式: C₁₈H₃₆N₂O₅
• 分子量: 360.494
• InChiKey: NITPYUIIKHECFI-UHFFFAOYSA-N

物化性质

• 沸点：
  484.1±38.0 °C(Predicted)
• 密度：
  1.040±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 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：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-tert-butoxycarbonylaminobutyl)(4-hydroxybutyl)carbamic acid tert-butyl ester 在 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 碘苯二乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以75%的产率得到{4-[tert-butoxycarbonyl-(4-oxo-butyl)-amino]-butyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Biological Properties of Quilamines II, New Iron Chelators with Antiproliferative Activities

  摘要：

  To selectively target tumor cells expressing an overactive Polyamine Transport System (PTS), we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, derived from the lead compound HQ1-44, which we named Quilamines II. The structures of four new antiproliferative agents were developed. They differ in the size of the linker (HQ0-44 and HQ2-44) or in the nature of the linker (HQCO-44 and HQCS-44) between a hydroxyquinoline moiety (HQ) and a homospermidine (44) chain, the best polyamine vector. The Quilamines II were obtained after 6 to 9 steps by Michael addition, peptide linkage, and reductive amination or by using the Willgerodt-Kindler reaction. The biological evaluation of these second-generation Quilamines showed that modifying the size of the linker increased the selectivity of these compounds for the PTS. In addition, measurement of the toxicity of Quilamines HQ0-44 and HQ2-44 highlighted their marked antiproliferative nature on several cancerous cell lines as well as a differential activity on nontransformed cells (fibroblasts). In contrast, Quilamines HQCO-44 and HQCS-44 presented low selectivity for the PTS, probably due to a loss of electrostatic interaction. We also demonstrated that the HCT116 cell line, originating from a human colon adenocarcinoma, was the most responsive to the various Quilamines. As deduced from the calcein and HVA assays, the higher iron chelating capacity of HQ1-44 could explain its higher antiproliferative efficiency.

  DOI：

  10.1021/bc4004734
• 作为产物：
  描述：

  4-(4-hydroxybutyl)aminobutanenitrile 在 ammonium hydroxide 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0 ℃ 、2.03 MPa 条件下， 反应 56.0h， 生成 (4-tert-butoxycarbonylaminobutyl)(4-hydroxybutyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Biological Properties of Quilamines II, New Iron Chelators with Antiproliferative Activities

  摘要：

  To selectively target tumor cells expressing an overactive Polyamine Transport System (PTS), we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, derived from the lead compound HQ1-44, which we named Quilamines II. The structures of four new antiproliferative agents were developed. They differ in the size of the linker (HQ0-44 and HQ2-44) or in the nature of the linker (HQCO-44 and HQCS-44) between a hydroxyquinoline moiety (HQ) and a homospermidine (44) chain, the best polyamine vector. The Quilamines II were obtained after 6 to 9 steps by Michael addition, peptide linkage, and reductive amination or by using the Willgerodt-Kindler reaction. The biological evaluation of these second-generation Quilamines showed that modifying the size of the linker increased the selectivity of these compounds for the PTS. In addition, measurement of the toxicity of Quilamines HQ0-44 and HQ2-44 highlighted their marked antiproliferative nature on several cancerous cell lines as well as a differential activity on nontransformed cells (fibroblasts). In contrast, Quilamines HQCO-44 and HQCS-44 presented low selectivity for the PTS, probably due to a loss of electrostatic interaction. We also demonstrated that the HCT116 cell line, originating from a human colon adenocarcinoma, was the most responsive to the various Quilamines. As deduced from the calcein and HVA assays, the higher iron chelating capacity of HQ1-44 could explain its higher antiproliferative efficiency.

  DOI：

  10.1021/bc4004734

文献信息

• Synthesis and Biological Evaluation of Dihydromotuporamine Derivatives in Cells Containing Active Polyamine Transporters
  作者：Navneet Kaur、Jean-Guy Delcros、Bénédicte Martin、Phanstiel

  DOI：10.1021/jm0491288

  日期：2005.6.1

  Dihydromotuporamine C (4) and its 4,4-triamine analogue (5) were synthesized in good yield using ring-closing metathesis (RCM) methods. Comparison of their biological activities (Ki determinations in L1210 cells and IC50 determinations in L1210, CHO, and CHO-MG cells) revealed that the motuporamine derivatives do not use the polyamine transporter (PAT) for cellular entry. Bioevaluation of a N1-(an

  使用闭环复分解（RCM）方法以高收率合成了二氢motuporamine C（4）及其4,4-三胺类似物（5）。比较它们的生物学活性（L1210细胞中的Ki测定和L1210，CHO和CHO-MG细胞中的IC50测定）表明，motuporamine衍生物不使用多胺转运蛋白（PAT）进入细胞。N1-（蒽-9-基甲基）-N1-（乙基）高嘧啶对照的生物评价（7）显示，N1叔胺中心的存在显着降低了多胺缀合物的PAT亲和力，并废除了其PAT-定位选择性。
• N-Substituent Effects in the Selective Delivery of Polyamine Conjugates into Cells Containing Active Polyamine Transporters
  作者：Richard Andrew Gardner、Jean-Guy Delcros、Fanta Konate、Fred Breitbeil、Bénédicte Martin、Michael Sigman、Min Huang、Phanstiel

  DOI：10.1021/jm0497040

  日期：2004.11.1

  N(1)-anthracen-9-ylmethyl, N(1)-2-(anthracen-9-yl)ethyl, N(1)-3-(anthracen-9-yl)propyl, and pyren-1-ylmethyl. The polyamine architecture was also altered and ranged from diamine to triamine and tetraamine systems. Biological activities in L1210 (murine leukemia), Chinese hamster ovary (CHO), and CHO's polyamine transport-deficient mutant (CHO-MG) cell lines were investigated via IC(50) cytotoxicity determinations

  合成了几种含有各种芳环系统的N（1）-芳基烷基多胺作为它们各自的HCl盐。评估的N（1）取代基大小从N（1）-苄基，N（1）-萘-1-基甲基，N（1）-2-（萘-1-基）乙基，N（1） -3-（萘-1-基）丙基，N（1）-蒽-9-基甲基，N（1）-2-（蒽-9-基）乙基，N（1）-3-（蒽-9 -基）丙基和pyr-1-基甲基。多胺的结构也被改变，范围从二胺到三胺和四胺体系。通过IC（50）细胞毒性测定研究了L1210（鼠白血病），中国仓鼠卵巢（CHO）和CHO的多胺转运缺陷型突变体（CHO-MG）细胞系的生物学活性。L1210细胞中亚精胺摄取的K（i）值也已确定。N（1）-芳基烷基取代基的大小以及所用的多胺序列直接影响到观察到的细胞毒性谱。如CHO / CHO-MG细胞毒性筛选所示，比乙烯长的N（1）-系链显示出对多胺转运蛋白（PAT）的选择性显着丧失。总之，对于N（1）取代基的大小有明确
• 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。