3-[7-(2-Cyanoethylamino)heptylamino]propanenitrile | 131275-74-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-[7-(2-Cyanoethylamino)heptylamino]propanenitrile
• 英文别名: 3-[7-(2-cyanoethylamino)heptylamino]propanenitrile
• CAS: 131275-74-6
• 化学式: C₁₃H₂₄N₄
• 分子量: 236.36
• InChiKey: QDGYCGRHRXRPHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  71.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[7-(2-Cyanoethylamino)heptylamino]propanenitrile 在 platinum(IV) oxide 盐酸 、 sodium hydroxide 、 potassium tert-butylate 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 24.0h， 生成 1,17-bis(phenylmethyl)-1,5,13,17-tetrakis(tert-butoxycarbonyl)-1,5,13,17-tetraazaheptadecane
  参考文献：
  名称：

  Antimalarial polyamine analogs

  摘要：

  A series of novel tetraamines of the general formula RNH(CH2)(x)NH(CH2)(y)(NH(CH2)(x)NHR was synthesized and examined for activity against growth of Plasmodium falciparum in vitro. Within the series, dibenzyl analogues (R = benzyl) were found to be the most effective growth inhibitors, with IC50 values of about 10-6 M. Further modifications of the tetraamine provided the optimum chain length for antimalarial activity of y = 7, x = 3. Compound 8 (MDL 27,695) with the structure y = 7, x = 3, R = benzyl, in combination with the ornithine decarboxylase inhibitor alpha-(difluoromethyl)ornithine, resulted in radical cures when tested against experimental Plasmodium berghei infections in mice. The structure-activity relationships of the series are discussed.

  DOI：

  10.1021/jm00106a015
• 作为产物：
  描述：

  1,7-二氨基庚烷 、 丙烯腈 以 乙醇 为溶剂， 生成 3-[7-(2-Cyanoethylamino)heptylamino]propanenitrile
  参考文献：
  名称：

  具有强抗疟活性的新型烷基化（双）脲和（双）硫脲多胺类似物的发现

  摘要：

  合成了一系列烷基化（双）脲和（双）硫脲多胺类似物，并在体外筛选了对氯喹敏感和耐药株恶性疟原虫的抗疟活性。所有类似物在小于 3 μM 时均显示出对恶性疟原虫的生长抑制活性，其中大多数具有100–650 nM 范围内的有效 IC 50值。由于核分裂和无性发育的阻滞，类似物在暴露后 24 小时内阻止了寄生生长。此外，这种作用似乎对疟原虫具有细胞毒性和高度选择性（对恶性疟原虫的IC 50低 7000 倍以上）) 并且通过多胺的外源加成是不可逆的。随着含有 3-7-3 或 3-6-3 个碳骨架和取代的末端脲或硫脲部分的多胺类似物的强效抗疟活性的首次报道，我们提出这些化合物代表了一类结构新颖的抗疟药。

  DOI：

  10.1021/jm200463z

文献信息

• (Bis)urea and (Bis)thiourea Inhibitors of Lysine-Specific Demethylase 1 as Epigenetic Modulators
  作者：Shiv K. Sharma、Yu Wu、Nora Steinbergs、Michael L. Crowley、Allison S. Hanson、Robert A. Casero、Patrick M. Woster

  DOI：10.1021/jm100217a

  日期：2010.7.22

  The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 overexpression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of isosteric ureas and thioureas that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2 and.transcription factor GATA4. These compounds represent an important new series of epigenetic modulators with the potential for use as antitumor agents.
• An approach to use an unusual adenosine transporter to selectively deliver polyamine analogues to trypanosomes
  作者：Ching-Kim Tye、Ganasan Kasinathan、Michael P. Barrett、Reto Brun、Valerie E. Doyle、Alan H. Fairlamb、Richard Weaver、Ian H. Gilbert

  DOI：10.1016/s0960-894x(98)00095-x

  日期：1998.4

  In this paper we describe an approach to selectively deliver compounds to trypanosomes using an adenosine transporter which is unique to the trypanosome. Various polyamine analogues have been attached to known substrates of this adenosine transporter. The compounds prepared interact specifically with the adenosine transporter, some with a similar efficiency to berenil, a known substrate. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Structural comparison of alkylpolyamine analogues with potent in vitro antitumor or antiparasitic activity
  作者：Frank H. Bellevue、Michelle Boahbedason、Ronghui Wu、Patrick M. Woster、Robert A. Casero、Donna Rattendi、Schennella Lane、Cyrus J. Bacchi

  DOI：10.1016/s0960-894x(96)00510-0

  日期：1996.11

  A series of symmetrically or unsymmetrically alkyl-substituted polyamine analogues were synthesized containing either a 3-3-3 or 3-7-3 polyamine backbone. These analogues were evaluated in vitro as antitumor agents in the NCI H157 and NCI H82 lung carcinoma cell lines, and as antitrypanosomal agents against four strains of Trypanosoma brucei brucei or Trypanosoma brucei rhodesiense. The resulting biological data suggest that it is possible to specifically target tumor cells or parasitic organisms with alkylpolyamine analogues based on structure. Copyright (C) 1996 Elsevier Science Ltd
• Discovery of Novel Alkylated (bis)Urea and (bis)Thiourea Polyamine Analogues with Potent Antimalarial Activities
  作者：Bianca K. Verlinden、Jandeli Niemand、Janette Snyman、Shiv K. Sharma、Ross J. Beattie、Patrick M. Woster、Lyn-Marie Birkholtz

  DOI：10.1021/jm200463z

  日期：2011.10.13

  A series of alkylated (bis)urea and (bis)thiourea polyamine analogues were synthesized and screened for antimalarial activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. All analogues showed growth inhibitory activity against P. falciparum at less than 3 μM, with the majority having effective IC50 values in the 100–650 nM range. Analogues arrested parasitic

  合成了一系列烷基化（双）脲和（双）硫脲多胺类似物，并在体外筛选了对氯喹敏感和耐药株恶性疟原虫的抗疟活性。所有类似物在小于 3 μM 时均显示出对恶性疟原虫的生长抑制活性，其中大多数具有100–650 nM 范围内的有效 IC 50值。由于核分裂和无性发育的阻滞，类似物在暴露后 24 小时内阻止了寄生生长。此外，这种作用似乎对疟原虫具有细胞毒性和高度选择性（对恶性疟原虫的IC 50低 7000 倍以上）) 并且通过多胺的外源加成是不可逆的。随着含有 3-7-3 或 3-6-3 个碳骨架和取代的末端脲或硫脲部分的多胺类似物的强效抗疟活性的首次报道，我们提出这些化合物代表了一类结构新颖的抗疟药。
• Antimalarial polyamine analogs
  作者：Michael L. Edwards、D. M. Stemerick、A. J. Bitonti、J. A. Dumont、P. P. McCann、P. Bey、A. Sjoerdsma

  DOI：10.1021/jm00106a015

  日期：1991.2

  A series of novel tetraamines of the general formula RNH(CH2)(x)NH(CH2)(y)(NH(CH2)(x)NHR was synthesized and examined for activity against growth of Plasmodium falciparum in vitro. Within the series, dibenzyl analogues (R = benzyl) were found to be the most effective growth inhibitors, with IC50 values of about 10-6 M. Further modifications of the tetraamine provided the optimum chain length for antimalarial activity of y = 7, x = 3. Compound 8 (MDL 27,695) with the structure y = 7, x = 3, R = benzyl, in combination with the ornithine decarboxylase inhibitor alpha-(difluoromethyl)ornithine, resulted in radical cures when tested against experimental Plasmodium berghei infections in mice. The structure-activity relationships of the series are discussed.