N-(3-(1,3-dioxoisoindolin-2-yl)propyl)-N-(2-(3,9-ditosyl-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)-4-methylbenzenesulfonamide | 1401006-68-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-(1,3-dioxoisoindolin-2-yl)propyl)-N-(2-(3,9-ditosyl-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)-4-methylbenzenesulfonamide
• CAS: 1401006-68-5
• 化学式: C₄₅H₅₀N₆O₈S₃
• 分子量: 899.125
• InChiKey: NKDLEWPIGYJQOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  62.0
• 可旋转键数：
  13.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  165.65
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N-(3-(1,3-dioxoisoindolin-2-yl)propyl)-N-(2-(3,9-ditosyl-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)-4-methylbenzenesulfonamide 在 肼 作用下， 以 乙醇 为溶剂， 生成 N-(3-aminopropyl)-N-(2-(3,9-ditosyl-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)-4-methylbenzenesulfonamide
  参考文献：
  名称：

  Synthetic single and double aza-scorpiand macrocycles acting as inhibitors of the antioxidant enzymes iron superoxide dismutase and trypanothione reductase in Trypanosoma cruzi with promising results in a murine model

  摘要：

  合成的类蝎子状氮杂大环化合物能选择性地抑制小鼠中的克鲁茨氏锥虫的SOD和TR酶，导致寄生虫死亡，并在感染和治疗后增加小鼠的存活率。

  DOI：

  10.1039/c4ra09866h
• 作为产物：
  描述：

  对甲苯磺酰氯 在 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 73.0h， 生成 N-(3-(1,3-dioxoisoindolin-2-yl)propyl)-N-(2-(3,9-ditosyl-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)-4-methylbenzenesulfonamide
  参考文献：
  名称：

  In vitro activity of scorpiand-like azamacrocycle derivatives in promastigotes and intracellular amastigotes of Leishmania infantum and Leishmania braziliensis

  摘要：

  The activity of a family scorpiand-like azamacrocycles against Leishmania infantum and Leishmania braziliensis was studied using promastigotes, axenic and intracellular amastigotes forms. All the compounds are more active and less toxic than meglumine antimoniate (Glucantime). Moreover, the data on infection rates and amastigotes showed that compounds P2Py, PN and P3Py are the most active against both species of Leishmania. On the other hand, studies on the inhibitory effect of these compounds on SOD enzymes showed that while the inhibition of the Fe-SOD enzyme of the promastigote forms of the parasites is remarkable, the inhibition of human CuZn-SOD and Mn-SOD from Escherichia coli is negligible. The ultrastructural alterations observed in treated promastigote forms confirmed that the compounds having the highest activity were those causing the largest cell damage. The modifications observed by H-1 NMR, and the amounts of catabolites excreted by the parasites after treatment with the compounds, suggested that the catabolic mechanism could depend on the structure of the side chains linked to the aza-scorpiand macrocycles. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.001

文献信息

• In vitro antileishmanial activity of aza-scorpiand macrocycles. Inhibition of the antioxidant enzyme iron superoxide dismutase
  作者：Clotilde Marín、Mario Inclán、Inmaculada Ramírez-Macías、M. Teresa Albelda、Rocio Cañas、Ma Paz Clares、Jorge González-García、Maria Jose Rosales、Kristina Urbanova、Enrique García-España、Manuel Sánchez-Moreno

  DOI：10.1039/c5ra21262f

  日期：——

  The in vitro leishmanicidal activity of a series of nine aza-scorpiand-like macrocycles, recently synthesized, was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, using promastigotes and intracellular amastigotes forms. The cytotoxicity of the tested compounds on J774.2 macrophage cells was also measured. Four of the tested compounds (1, 2, 8 and 9) showed

  在体外的一系列的leishmanicidal活动9氮杂scorpiand状的大环化合物，最近合成，于测试婴儿利什曼原虫，巴西利什曼原虫和杜氏利什曼原虫寄生虫，利用前鞭毛体和胞内无鞭毛体形式。还测量了测试化合物对J774.2巨噬细胞的细胞毒性。测试化合物（四个1，2，8和9）显示出选择性指标比参考药物Glucantime的三个较高利什曼原虫种。此外，有关感染率和变形虫的数据表明，化合物1，2，8和9是针对这三种中最活跃的利什曼原虫属物种。与四个化合物（治疗寄生虫的排泄产物分布的变化1，2，8和9）也具有大量细胞质的改变相一致。另一方面，在所考虑的三种寄生虫物种中，活性最高的化合物是Fe-SOD的有效抑制剂，而它们对人CuZn-SOD的影响却很低。起始原料的高活性，低毒性，稳定性，低成本和简单的合成方法使这些化合物成为开发负担得起的抗杀菌剂的分子。
• Modulation of DNA Binding by Reversible Metal-Controlled Molecular Reorganizations of Scorpiand-like Ligands
  作者：Mario Inclán、M. Teresa Albelda、Juan C. Frías、Salvador Blasco、Begoña Verdejo、Carolina Serena、Clàudia Salat-Canela、Maria Luisa Díaz、Antonio García-España、Enrique García-España

  DOI：10.1021/ja300538s

  日期：2012.6.13

  DNA interaction with scorpiand azamacrocycles has been achieved through modulation of their binding affinities. Studies performed with different experimental techniques provided evidence that pH or metal-driven molecular reorganizations of these ligands regulate their ability to interact with calf thymus DNA (ctDNA) through an intercalative mode. Interestingly enough, metal-driven molecular reorganizations serve to increase or decrease the biological activities of these compounds significantly.
• Scorpiand-like azamacrocycles prevent the chronic establishment of Trypanosoma cruzi in a murine model
  作者：Francisco Olmo、Clotilde Marín、M. Paz Clares、Salvador Blasco、M. Teresa Albelda、Conxa Soriano、Ramón Gutiérrez-Sánchez、Francisco Arrebola-Vargas、Enrique García-España、Manuel Sánchez-Moreno

  DOI：10.1016/j.ejmech.2013.09.048

  日期：2013.12

  Chagas disease is today one of the most important neglected diseases for its upcoming expansion to nonendemic areas and has become a threat to blood recipients in many countries. In this study, the trypanocidal activity of ten derivatives of a family of aza-scorpiand like macrocycles is evaluated against Thypanosoma cruzi in vitro and in vivo murine model in which the acute and chronic phases of Chagas disease were analyzed. The compounds 4, 3 and 1 were found to be more active against the parasite and less toxic against Vero cells than the reference drug benznidazole, 4 being the most active compound, particularly in the chronic phase. While all these compounds showed a remarkable degree of inhibition of the Fe-SOD enzyme of the epimastigote forms of T cruzi, they produced a negligible inhibition of human CuZn-SOD and Mn-SOD from Escherichia coli. The modifications observed by H-1 NMR and the amounts of excreted catabolites by the parasites after treatment suggested that the mechanism of action could be based on interactions of the side chains of the compounds with enzymes of the parasite metabolism. The ultrastructural alterations observed in treated epimastigote forms confirmed that the compounds having the highest activity are those causing the largest cell damage. A complementary histopathological analysis confirmed that the compounds tested were significantly less toxic to mammals than the reference drug. (C) 2013 Elsevier Masson SAS. All rights reserved.