N-(7-氯-4-喹啉基)-N'-[2-[(7-氯-4-喹啉基)氨基]乙基]-1,2-乙二胺 | 215592-20-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: N-(7-氯-4-喹啉基)-N'-[2-[(7-氯-4-喹啉基)氨基]乙基]-1,2-乙二胺
• 中文别名: N-（7-氯-4-喹啉基）-N'-[2-[（7-氯-4-喹啉基）氨基]乙基]-1,2-乙二胺
• 英文名称: N1-(7-chloroquinolin-4-yl)-N2-(2-((7chloroquinolin-4-yl)amino)ethyl)ethane-1,2-diamine
• 英文别名: 7-chloro-N-{2-[(7-chloroquinolin-4-yl-)amino]ethyl}quinolin-4-amine；bisaminoquinoline；N-(7-Chloro-4-quinolinyl)-N'-[2-[(7-chloro-4-quinolinyl)amino]ethyl]-1,2-ethanediamine；N'-(7-chloroquinolin-4-yl)-N-[2-[(7-chloroquinolin-4-yl)amino]ethyl]ethane-1,2-diamine
• CAS: 215592-20-4
• 化学式: C₂₂H₂₁Cl₂N₅
• 分子量: 426.348
• InChiKey: HRUWSRXSOBVXEI-UHFFFAOYSA-N

物化性质

• 沸点：
  676.6±55.0 °C(Predicted)
• 密度：
  1.376±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  61.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(7-氯-4-喹啉基)-N'-[2-[(7-氯-4-喹啉基)氨基]乙基]-1,2-乙二胺 在 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 6-氯-1-羟基苯并三氮唑 、 肼 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 85.0h， 生成
  参考文献：
  名称：

  [EN] BIAMINOQUINOLINES AND NANOFORMULATIONS FOR CANCER TREATMENT
  [FR] BIAMINOQUINOLINES ET NANOFORMULATIONS POUR LE TRAITEMENT DU CANCER

  摘要：

  本发明提供了式（I）的双氨基喹啉化合物。本发明还提供了包含本发明化合物的纳米载体，以及利用这些纳米载体用于治疗疾病和成像的方法。

  公开号：

  WO2021055705A1
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 反应 2.5h， 以56.1%的产率得到N-(7-氯-4-喹啉基)-N'-[2-[(7-氯-4-喹啉基)氨基]乙基]-1,2-乙二胺
  参考文献：
  名称：

  Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme

  摘要：

  Based on the idea that compounds designed to exhibit high affinity for heme would block hemozoin formation, a critical heme-detoxification process for malarial parasites, we synthesized a series of compounds with two pi-conjugated moieties at terminal amino groups of triamine. These compounds exhibited moderate to high antimalarial activities in vitro toward both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. In a P. berghei-infected mouse model, 3a and 12a showed potent antimalarial activities compared to artesunate, as well as a prolonged duration of antimalarial effect. We found a good correlation between protective activity against hemin degradation and antimalarial activity. Compounds 8b and 3a strongly inhibited hemozoin formation catalyzed by heme detoxification protein.

  DOI：

  10.1021/acsmedchemlett.8b00222

文献信息

• Bisquinolines. 2. Antimalarial <i>N</i>,<i>N</i>-Bis(7-chloroquinolin-4-yl)heteroalkanediamines
  作者：Jonathan L. Vennerstrom、Arba L. Ager,、Arnulf Dorn、Steven L. Andersen、Lucia Gerena、Robert G. Ridley、Wilbur K. Milhous

  DOI：10.1021/jm9803828

  日期：1998.10.1

  berghei in vivo. These bisquinolines had IC50 values from 1 to 100 nM against P. falciparum in vitro. Six of the 11 bisquinolines were significantly more potent against the chloroquine-resistant W2 clone compared to the chloroquine-sensitive D6 clone. For bisquinolines 1-11 there was no relationship between the length of the bisquinoline heteroalkane bridge and antimalarial activity and no correlation

  合成了N，N-双（7-氯喹啉-4-基）杂烷二胺1-11，并在体外和体外对恶性疟原虫进行了筛选。这些双喹啉在体外对恶性疟原虫的IC50值为1至100 nM。与对氯喹敏感的D6克隆相比，在11种双喹啉中有6种对耐氯喹的W2克隆的效价明显更高。对于双喹啉1-11，双喹啉杂烷烃桥的长度与抗疟活性之间没有关系，并且在体内和体外抗疟活性之间也没有相关性。在体内，具有烷基醚和哌嗪桥的双喹啉比具有烷基胺桥的双喹啉对伯氏疟原虫有效。Bisquinolines 1-10是血凝素聚合的有效抑制剂，IC50值在5-20 microM的狭窄范围内，在抑制血凝素聚合的能力和抑制寄生虫生长之间存在相关性。与烷烃桥联的双喹啉相比（Vennerstrom等人，1992），这些杂烷烃桥联的双喹啉没有一个具有足够的抗疟活性，因此值得对该系列进行进一步研究。
• Synthesis and in vitro antimalarial activity of a series of bisquinoline and bispyrrolo[1,2a]quinoxaline compounds
  作者：Lezanne van Heerden、Theunis T. Cloete、J. Wilma Breytenbach、Carmen de Kock、Peter J. Smith、Jaco C. Breytenbach、David D. N’Da

  DOI：10.1016/j.ejmech.2012.07.037

  日期：2012.9

  Series of bisquinolines 4–15 and bispyrrolo[1,2a]quinoxalines 16–20 containing various polyamine linkers were synthesized. The aqueous solubility and distribution coefficient were experimentally determined. The compounds were screened for antimalarial activity alongside chloroquine against D10 and Dd2 strains of Plasmodium falciparum. The growth inhibitory effects of biscompounds 4–9 were assessed

  合成了含有各种多胺连接基的一系列双喹啉4-15和双吡咯并[1,2a]喹喔啉16-20。通过实验确定了水溶性和分布系数。筛选了化合物和氯喹对恶性疟原虫的D10和Dd2菌株的抗疟活性。对多种癌细胞系评估了双化合物4–9的生长抑制作用。发现水溶性随着潜在的质子化位点的增加而增加。双喹啉8和9分别具有三亚乙基四胺和N，N'-双（3-氨基丙基）乙二胺连接基的化合物是所有合成化合物中活性最高的。发现它们对氯丹抗D10一样有效，但对Dd2菌株则更有效，对寄生细胞具有良好的选择性。含有二亚乙基三胺桥的化合物4显示了该系列中最重要的抗癌活性，并且比依托泊苷对所有三种TK10，UACC62和MCF7癌细胞系均具有更有效的抗增殖抑制剂。
• Antiplasmodial Activity and Cytotoxicity of Bis-, Tris-, and Tetraquinolines with Linear or Cyclic Amino Linkers
  作者：Sophie Girault、Philippe Grellier、Amaya Berecibar、Louis Maes、Pascal Lemière、Elisabeth Mouray、Elisabeth Davioud-Charvet、Christian Sergheraert

  DOI：10.1021/jm001096a

  日期：2001.5.1

  Bisquinoline heteroalkanediamines were structurally modified in order to study the effects of enhanced bulkiness and rigidity on both their activity on strains of Plasmodium falciparum expressing different degrees of chloroquine (CQ) resistance and their cytotoxicity toward mammalian cells. While cyclization yielded molecules of greater rigidity that were not more active than their linear counterparts, they were characterized by an absence of cytotoxicity. Alternatively, dimerization of these compounds led to tetraquinolines that are very potent for CQ-resistant strains and noncytotoxic.
• Anticancer properties of bisaminoquinolines with modified linkers
  作者：Yuanhao Wang、Vaibhav Jain、Amanda Versace、Monika Bhardwaj、Mary Ann S. Crissey、Ravi K. Amaravadi、Jeffrey D. Winkler

  DOI：10.1016/j.bmcl.2021.128272

  日期：2021.10
• A pH‐Driven Small‐Molecule Nanotransformer Hijacks Lysosomes and Overcomes Autophagy‐Induced Resistance in Cancer
  作者：Zhao Ma、Kai Lin、Menghuan Tang、Mythili Ramachandran、Reng Qiu、Jin Li、Lucas N. Solano、Yanyu Huang、Cristabelle De Souza、Sara Abou‐Adas、Bai Xiang、Lanwei Zhang、Minyong Li、Yuanpei Li

  DOI：10.1002/anie.202204567

  日期：2022.8.26

  AbstractSmart conversion of supramolecular structures in vivo is an attractive strategy in cancer nanomedicine, which is usually achieved via specific peptide sequences. Here we developed a lysosomal targeting small‐molecule conjugate, PBC, which self‐assembles into nanoparticles at physiological pH and smartly converts to nanofibrils in lysosomes of tumor cells. Such a transformation mechanically leads to lysosomal dysfunction, autophagy inhibition, and unusual cytoplasmic vacuolation, thus granting PBC a unique anticancer activity as a monotherapy. Importantly, the photo‐activated PBC elicits significant phototoxicity to lysosomes and shows enormous advantages in overcoming autophagy‐caused treatment resistance frequently occurring in conventional phototherapy. This improved phototherapy achieves a complete cure of oral cancer xenografts upon limited administration. Our work provides a new paradigm for the construction of nonpeptide nanotransformers with biomedical activities.