CGC-11047 | 308145-19-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: CGC-11047
• 英文别名: N,N'-bis(3-ethylaminopropyl)-cis-but-2-ene-1,4-diamine；CGC-11047 free base；(Z)-N,N'-bis[3-(ethylamino)propyl]but-2-ene-1,4-diamine
• CAS: 308145-19-9
• 化学式: C₁₄H₃₂N₄
• 分子量: 256.435
• InChiKey: XFWLTFZLLXVKDY-WAYWQWQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  48.1
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-乙基-1,3-丙二胺 在 sodium hydroxide 、 氢溴酸 、 sodium hydride 、 溶剂黄146 、 苯酚 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 71.0h， 生成 CGC-11047
  参考文献：
  名称：

  Conformationally Restricted Analogues of ¹N,¹²N-Bisethylspermine:  Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines

  摘要：

  Eight analogues of N-1,N-12-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1,2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained.(three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). N-1,N-12-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the N-4,N-9-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1,2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.

  DOI：

  10.1021/jm980172v

文献信息

• Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents
  作者：Diptesh Sil、Sudipta Panja、Chinmay M. Jogdeo、Raj Kumar、Ao Yu、Cassandra E. Holbert、Ling Ding、Jackson R. Foley、Tracy Murray Stewart、Robert A. Casero、David Oupický

  DOI：10.3390/molecules27082441

  日期：——

  Conformationally restrained polyamine analog PG11047 is a well-known drug candidate that modulates polyamine metabolism and inhibits cancer cell growth in a broad spectrum of cancers. Here, we report a structure–activity relationship study of the PG11047 analogs (HPGs) containing alkyl chains of varying length, while keeping the unsaturated spermine backbone unchanged. Synthesis of higher symmetrical

  构象受限的多胺类似物 PG11047 是一种众所周知的候选药物，可调节多胺代谢并抑制广谱癌症中的癌细胞生长。在这里，我们报告了包含不同长度烷基链的 PG11047 类似物 (HPG) 的结构-活性关系研究，同时保持不饱和精胺骨架不变。通过比之前的 PG11047 路线更少步骤的合成路线实现了更高对称同系物的合成。两亲性 HPG 类似物经过自组装形成球形纳米颗粒，其尺寸随着疏水烷基链长度的增加而增加。体外抗癌活性评估显示，与 PG11047 相比，具有较长烷基链的类似物在人结肠癌细胞系 HCT116 中的癌细胞抑制活性增加了 8 倍以上，在人肺中增加了 10 倍以上癌细胞系 A549。对精胺氧化酶 (SMOX) 抑制的评估表明，PG11047 没有活性，但观察到其较高对称同系物的活性。与参考 SMOX 抑制剂 MDL72527 的比较显示，性能最佳的 HPG 类似物的活性提高了 9 倍。
• Treatment and prevention of vascular hyperplasia using polyamine and polyamine analog compounds
  申请人：Marton J. Laurence

  公开号：US20070232677A1

  公开（公告）日：2007-10-04

  This disclosure relates to methods of inhibiting vascular hyperplasia using polyamines, polyamine analogs, and conformationally restricted polyamine analogs, or a conjugate of a polyamine, polyamine analog, or conformationally restricted polyamine analog. Polyamines, polyamine analogs, conformationally restricted polyamine analogs, and conjugates thereof are useful in reducing stenosis and restenosis of blood vessels and grafts.

  本公开涉及使用多胺，多胺类似物和构象限制多胺类似物或多胺，多胺类似物或构象限制多胺类似物的共轭物来抑制血管增生的方法。多胺，多胺类似物，构象限制多胺类似物及其共轭物在减少血管和移植物的狭窄和再狭窄方面非常有用。
• NOVEL POLYAMINE ANALOG CONJUGATES AND QUINONE CONJUGATES AS THERAPIES FOR CANCERS AND PROSTATE DISEASES
  申请人：FRYDMAN Benjamin

  公开号：US20090275664A1

  公开（公告）日：2009-11-05

  Peptide conjugates in which cytocidal and cytostatic agents, such as polyamine analogs or naphthoquinones, are conjugated to a polypeptide recognized and cleaved by enzymes such as prostate-specific antigen (PSA) and cathepsin B are provided, as well as compositions comprising these conjugates. Methods of using these conjugates in the treatment of prostate diseases are also provided.

  本发明涉及肽共轭物，其中细胞毒和细胞增殖抑制剂，如多胺类似物或萘醌类化合物，与识别和剪切酶（如前列腺特异性抗原（PSA）和cathepsin B）识别的多肽共轭，以及包含这些共轭物的组合物。本发明还提供了使用这些共轭物治疗前列腺疾病的方法。
• COMPOSITIONS AND METHODS FOR TRANSPORT OF MOLECULES WITH ENHANCED RELEASE PROPERTIES ACROSS BIOLOGICAL BARRIERS
  申请人：Wender Paul A

  公开号：US20100255499A1

  公开（公告）日：2010-10-07

  Conjugates of a cargo molecule with a transporter molecule are disclosed, where the cargo molecule and the transporter molecule are linked covalently by a releasable linker. The cargo of the conjugate can be a biologically active agent or a reporter molecule. The transporter modulates the transport of the cargo across a biological barrier (e.g., a cell membrane) compared to the transport of the unconjugated cargo. Releasable linkers suitable for rapid and facile conjugation to various types of cargo and transporters are also disclosed, along with methods for using the linkers in the synthesis of conjugates.

  本发明公开了一种货物分子与运输蛋白分子的共轭体，其中货物分子和运输蛋白分子通过可释放的连接剂共价连接。共轭体的货物可以是生物活性剂或报告分子。与未共轭货物的运输相比，运输蛋白调节货物通过生物屏障（例如细胞膜）的运输。还公开了适用于快速和容易地与各种类型的货物和运输蛋白共轭的可释放连接剂，以及使用连接剂合成共轭体的方法。
• MITOGUAZONE FOR PREVENTING THE RELAPSE OR THE PROGRESSION OF MULTIPLE SCLEROSIS
  申请人：Pathologica LLC

  公开号：EP3831372A1

  公开（公告）日：2021-06-09

  Disclosed herein are new oral pharmaceutical compositions of SAMDC inhibitors, polyamine analogs, and polyamine biosynthesis inhibitors, and their application for the treatment of conditions including demyelinating diseases, autoimmune disorders affecting the nervous system, and other neurodegenerative conditions.

  本文公开了SAMDC抑制剂、多胺类似物和多胺生物合成抑制剂的新型口服药物组合物，以及它们在治疗脱髓鞘疾病、影响神经系统的自身免疫性疾病和其他神经退行性疾病等疾病中的应用。