3,3'-[N,N'-[(methylimino)di-3,1-propanediyldiimino]]bis(4-ethoxy-3-cyclobutene-1,2-dione) | 679427-49-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3,3'-[N,N'-[(methylimino)di-3,1-propanediyldiimino]]bis(4-ethoxy-3-cyclobutene-1,2-dione)
• 英文别名: N,N-bis-[3-(2-ethoxy-3,4-dioxo-1-cyclobutenyl)-aminopropyl]methylamine；3-Ethoxy-4-[3-[3-[(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]propyl-methylamino]propylamino]cyclobut-3-ene-1,2-dione；3-ethoxy-4-[3-[3-[(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]propyl-methylamino]propylamino]cyclobut-3-ene-1,2-dione
• CAS: 679427-49-7
• 化学式: C₁₉H₂₇N₃O₆
• 分子量: 393.44
• InChiKey: OIZCIODSVOSKSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3,3'-[N,N'-[(methylimino)di-3,1-propanediyldiimino]]bis(4-ethoxy-3-cyclobutene-1,2-dione) 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  A squaramide fluorescent ensemble for monitoring sulfate in water

  摘要：

  提出了一种简单的分子传感器，该传感器利用了包含在一个阴离子识别位点内的两个磺酰胺单元独特的猝灭和结合能力，用于监测水中的硫酸盐。

  DOI：

  10.1039/b104172j
• 作为产物：
  描述：

  N,N-双(3-氨丙基)甲胺 、 方酸二乙酯 以 乙醚 为溶剂， 以74%的产率得到3,3'-[N,N'-[(methylimino)di-3,1-propanediyldiimino]]bis(4-ethoxy-3-cyclobutene-1,2-dione)
  参考文献：
  名称：

  Evidence of anion-induced dimerization of a squaramide-based host in protic solvents

  摘要：

  将磺酰亚胺单元与四烷基铵基团结合，得到了两种在水-乙醇混合物中能特异性结合双阴离子的主体分子。通过ITC、荧光和1H NMR数据支持了主体2与客体形成2:1化学计量比的络合物。

  DOI：

  10.1039/b614172b

文献信息

• Cyclosquaramides as Kinase Inhibitors with Anticancer Activity
  作者：Priam Villalonga、Silvia Fernández de Mattos、Guillem Ramis、Antònia Obrador-Hevia、Angel Sampedro、Carmen Rotger、Antoni Costa

  DOI：10.1002/cmdc.201200157

  日期：2012.8

  phosphorylation, as compounds 7 and 8 are effective inhibitors of several important kinases such as ABL1, CDK4, CHK1, PKC, c‐MET, and FGFR, among others. The corresponding acyclic oligosquaramides and smaller cyclosquaramides did not show antitumor activity, suggesting that a macrocyclic structure with minimal molecular size plays a key role in the observed antitumor activity.

  我们报告了一系列新的基于低聚四酰胺的大环化合物作为抗癌剂的合成和生物学评估。化合物7被认为是该系列的代表，对NCI-60人类肿瘤细胞系显示出显着的抗增殖活性，IC 50值为1至10μM。结果表明，对环四酰胺的敏感性明显取决于细胞类型，从而强调了一定程度的生物选择性。作为化合物7和8，观察到的抗增殖作用似乎与蛋白磷酸化的失调有关。是几种重要激酶的有效抑制剂，如ABL1，CDK4，CHK1，PKC，c-MET和FGFR等。相应的无环低聚酰胺和较小的环聚酰胺没有显示抗肿瘤活性，这表明具有最小分子大小的大环结构在观察到的抗肿瘤活性中起关键作用。
• USE OF CYCLOSQUARAMIDE COMPOUNDS AS ANTI-TUMOUR AGENTS
  申请人：Costa Torres Antonio

  公开号：US20110294772A1

  公开（公告）日：2011-12-01

  Use of squaramide-based macrocylic compounds as kinase inhibitor agents and as anti-tumour agents. More specifically, said compounds are used to treat diseases such as cancer, diabetes, neurodegenerative diseases, HIV replication, etc. Furthermore, the present invention likewise relates to pharmaceutical compositions that contain said compounds

  使用基于方酰胺的大环化合物作为激酶抑制剂和抗肿瘤剂。更具体地，所述化合物被用于治疗癌症、糖尿病、神经退行性疾病、HIV复制等疾病。此外，本发明还涉及含有所述化合物的药物组合物。
• Synthesis and Biological Evaluation of <i>N</i>,<i>N</i>′-Squaramides with High in Vivo Efficacy and Low Toxicity: Toward a Low-Cost Drug against Chagas Disease
  作者：Francisco Olmo、Carmen Rotger、Inmaculada Ramírez-Macías、Luis Martínez、Clotilde Marín、Lucas Carreras、Kristína Urbanová、Manel Vega、Guillermo Chaves-Lemaur、Angel Sampedro、María Jose Rosales、Manuel Sánchez-Moreno、Antonio Costa

  DOI：10.1021/jm4017015

  日期：2014.2.13

  Access to basic drugs is a major issue in developing countries. Chagas disease caused by Trypanosorna cruzi is a paradigmatic example of a chronic disease without an effective treatment. Current treatments based on benznidazole and nifurtimox are expensive, ineffective, and toxic. N,N'-Squaramides are amide-type compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites. When combined with amine and carboxylic groups, squaramide compounds have increased solubility and therefore make suitable therapeutic agents. In this work, we introduce a group of Lipiriski's rule of five compliant squararnides as candidates for treating Chagas disease. The in vivo studies confirmed the positive expectations arising from the preliminary in vitro studies, revealing compound 17 to be the most effective for both acute and chronic phases. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-Chagasic agent.
• Efficient Macrocyclization of Preorganized Palindromic Oligosquaramides
  作者：Carmen Rotger、M. Neus Piña、Manuel Vega、Pablo Ballester、Pere M. Deyà、Antoni Costa

  DOI：10.1002/anie.200602790

  日期：2006.10.20
• Conformational Preferences and Self-Template Macrocyclization of Squaramide-Based Foldable Modules
  作者：M. Carmen Rotger、M. Neus Piña、Antonio Frontera、Gabriel Martorell、Pablo Ballester、Pere M. Deyà、Antoni Costa

  DOI：10.1021/jo035546t

  日期：2004.4.1

  Secondary squaramides have considerable potential as hydrogen bond donors and acceptors. In CHCl3 both, anti- and syn-squaramide rotamers are observed by NMR. The energetic barrier for anti/syn mutual interconversion determined by complete band shape analysis is similar to63 kJ mol(-1). As in proline derivatives, a low rotational barrier is crucial for the design of foldable modules. In this paper, folding based on the low rotational barrier of squaramides is driven by donor atoms (N or O) located in the gamma position of an alkyl chain of a secondary squaramide. We demonstrate that the resulting minimal module exists as a folded conformer through the formation of a nine-membered ring stabilized by intramolecular hydrogen bonding. Molecular mechanics calculations and NMR studies support the existence of these folded conformers. The intramolecularly hydrogen bonded conformers are clearly visible even in CHCl3-EtOH mixtures. Folding occurs even in pure ethanol. As an indirect test, we studied the effectiveness of macrocyclization reactions in pure ethanol that require an effective templating effect to take place. The high yields obtained support the dominant role of a folded conformer even in this solvent.