tert-butyl (4-(tert-butoxycarbonylamino)butyl)(3-cyanopropyl)carbamate | 705281-90-9

• 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: tert-butyl (4-(tert-butoxycarbonylamino)butyl)(3-cyanopropyl)carbamate
• 英文别名: (4-tert-Butoxycarbonylamino-butyl)-(3-cyano-propyl)-carbamic acid tert-butyl ester；tert-butyl N-(3-cyanopropyl)-N-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]carbamate
• CAS: 705281-90-9
• 化学式: C₁₈H₃₃N₃O₄
• 分子量: 355.478
• InChiKey: STNSTVZQIAISIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  91.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-(tert-butoxycarbonylamino)butyl)(3-cyanopropyl)carbamate 在 氨 、 氢气 、 镍 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 以95%的产率得到tert-butyl (4-aminobutyl)(4-((tert-butoxycarbonyl)amino)butyl)carbamate
  参考文献：
  名称：

  Petrobactin及其同系物作为潜在的增长刺激的全合成为Marinobacter ^ h ydrocarbonoclasticus，油降解菌

  摘要：

  一种模块化合成的开发是为了访问petrobactin，含儿茶酚铁载体分离自Marinobacter hydrocarbonoclasticus。还合成了一系列具有不同二羟基苯甲酰胺基序的石油robactin同源物，在一种情况下，还合成了多胺主链中增加的碳数。因此，这些系统代表了新的异构探针，用于研究碳氢解质支原体中铁的运输性质。报道了石油链菌素及其同系物的合成以及这些药剂如何影响烃裂枝分枝杆菌的生长的首次生物学研究。开发了新的合成方法来克服早期合成中遇到的问题（酰亚胺形成）。两者都1石蜡肌动蛋白的1 H和13 C NMR与最近修订的结构一致，表明该石蜡肌动蛋白实际上包含3,4-二羟基苯基序而不是2,3-二羟基苯基序。初步的生物研究表明，使用本机petrobactin 1B为M. hydrocarbonoclasticus特异性生长刺激可能对溢油清理一个贫穷的战略。

  DOI：

  10.1021/jo049803l
• 作为产物：
  描述：

  N-叔丁氧羰基-1,4-丁二胺 在 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 32.0h， 生成 tert-butyl (4-(tert-butoxycarbonylamino)butyl)(3-cyanopropyl)carbamate
  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

• 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。
• METAL-CHELATING COMPOUNDS HAVING AT LEAST ONE POLYAMINO CHAIN
  申请人：UNIVERSITE DE RENNES I

  公开号：US20140364454A1

  公开（公告）日：2014-12-11

  The invention relates to metal-chelating compounds comprising one or more 8-hydroxyquinoline units substituted in position 2 with a nitrogenous group comprising a polyamino chain, wherein the polyamino chain is N-substituted on said nitrogenous group, to the composition containing same, and to the uses thereof in the therapeutic field and in particular in the treatment of diseases associated with an abnormality in the regulation of metal metabolism resulting in a metal overload in human or animal cells.

  该发明涉及含有一个或多个8-羟基喹啉单元的金属螯合化合物，该单元在位置2上被一种氮杂基取代，该氮杂基包括一个聚氨基链，在所述氮杂基上N-取代的聚氨基链，以及含有该化合物的组合物，以及在治疗领域中的用途，特别是在治疗与金属代谢调节异常导致人类或动物细胞中金属超载相关的疾病的用途。
• Lipophilic polyamines providing enhanced intracellular delivery of agents by a polyamine transport system
  申请人：University of Central Florida Research Foundation, Inc.

  公开号：US07910363B1

  公开（公告）日：2011-03-22

  Polyamine cationic lipids have been synthesized that have the ability to be transported into cells having an active polyamine transport system. Accordingly, these lipids may be conjugated with various agents and, thereby, act as vectors for transporting the agent into the cell aided by the cell's own polyamine transport system. A method of delivering an agent into a cell includes associating the agent with a polyamine cationic lipid selected from compounds 25, 26, 27, 28, their pharmaceutically acceptable salts and combinations thereof and contacting the cell therewith.

  合成了具有运输到具有活性多胺转运系统的细胞的能力的聚胺阳离子脂质。因此，这些脂质可以与各种药剂结合，并作为向细胞运输药剂的载体，利用细胞自身的多胺转运系统。将药剂与从化合物25、26、27、28及其药学上可接受的盐和其组合物中选择的多胺阳离子脂质关联，并与细胞接触的方法可将药剂传递到细胞中。
• Targeting the Polyamine Transport System with Benzazepine- and Azepine-Polyamine Conjugates
  作者：Sophie Tomasi、Jacques Renault、Bénédicte Martin、Stephane Duhieu、Virginie Cerec、Myriam Le Roch、Philippe Uriac、Jean-Guy Delcros

  DOI：10.1021/jm1007648

  日期：2010.11.11

  The polyamine transport system (PTS) whose activity is up-regulated in cancer cells is an attractive target for drug design. Two heterocyclic (azepine and benzazepine) systems were conjugated to various polyamine moieties through an amidine bound to afford 18 compounds which were evaluated for their affinity for the PTS and their ability to use the PTS for cell delivery. Structure-activity relationship studies and lead optimization afforded two attractive PTS targeting compounds. The azepine-spermidine conjugate 14 is a very selective substrate of the PTS that may serve as a vector for radioelements used for diagnoses or therapeutics in nuclear medicine. The nitrobenzazepine-spermine conjugate 28 is a very powerful PTS inhibitor with very low intrinsic cytotoxicity, able to prevent the growth of polyamine depleted cells in presence of exogenous polyamines.