4-nitrophenyl benzo[f][1,2,3,4,5]pentathiepine-7-carboxylate | 1240485-63-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 4-nitrophenyl benzo[f][1,2,3,4,5]pentathiepine-7-carboxylate
• 英文别名: (4-Nitrophenyl) 1,2,3,4,5-benzopentathiepine-7-carboxylate
• CAS: 1240485-63-5
• 化学式: C₁₃H₇NO₄S₅
• 分子量: 401.533
• InChiKey: PWPGOUJVFYYZJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  199
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-nitrophenyl benzo[f][1,2,3,4,5]pentathiepine-7-carboxylate 、 L-赤式-鞘氨醇 以 四氢呋喃 为溶剂， 反应 24.0h， 以21%的产率得到N-((2R,3S,E)-1,3-dihydroxyoctadec-4-en-2yl)benzo[f][1,2,3,4,5]pentathiepine-7-carboxamide
  参考文献：
  名称：

  Synthesis and antiproliferative properties of a new ceramide analog of varacin

  摘要：

  A benzopentasulfane was synthesized in 8 steps with a ceramide attached through an amide bond to the 7-position of the heterocycle structure. The anticancer activity of this synthetic ceramide-benzopolysulfane drug conjugate was analyzed against five human cancer cell lines MDA-MB-231 (breast), DU145 (prostate), MIA PaCa-2 (pancreas), HeLa (cervix), and U251 (glioblastoma). The ceramide-benzopolysulfane conjugate had IC50 values ranging from 10 to >20 mu M with complete cell killing at 12.5 mu M for MDA-MB-231 and 20 mu M for DU145 and HeLa cells. The ceramide-benzopolysulfane conjugate had IC50 values 1.8 and 4.0 times lower than a PEG benzopolysulfane, N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzo[f][1,2,3,4,5]-pentathiepine-7-carboxamide, for MDA-MB-231 and DU145 cells, respectively. The parent "unsubstituted" benzopolysulfane, o-C6H4S5, had IC50 values 4.2 times lower and 2.7 times higher than the ceramide benzopolysulfane for MDA-MB-231 and DU145 cells, respectively. The results indicate that the polysulfur linkage is needed for activity since benzenedithiol, o-C6H4(SH)(2), had IC50 values greater than 30 mu M with little effect on MDA-MB-231 and DU145 cells. Thus, to account for the bioactivity, a bimolecular reaction of cellular thiol with the ceramide benzopolysulfane is a proposed followed by thiozone (S-3) extrusion. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.chemphyslip.2015.07.023
• 作为产物：
  描述：

  3,4-dimercaptobenzoic acid 在 二氯化二硫 、 4-二甲氨基吡啶 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.25h， 生成 4-nitrophenyl benzo[f][1,2,3,4,5]pentathiepine-7-carboxylate
  参考文献：
  名称：

  穿透细胞的动态共价苯并聚砜网络

  摘要：

  环状寡硫属化合物（COC）有望成为渗透细胞的有前途的系统。明显优于和不同于已报道的二硒代壬二烯和表二硫代二酮哌嗪，我们引入了苯并多硫烷（BPS），它们显示出有效的递送，对内吞作用抑制剂的不敏感性以及与蛋白质一样大的底物的相容性。这种高活性与选择性地对硫醇的高反应性相吻合，超过了二硫化物在张力下的交换速率。其结果是形成了一个动态的共价网络，其中包括从二聚体到七聚体的最高硫物种，包括环状低聚物，环中最多包含19个硫。然后，从这个不断发展的自适应网络中进行选择，即可获得进入新的吸收途径所需的反应性和选择性。与其他COC相反，BPS在硫醇亲和柱上显示出很高的保留率。

  DOI：

  10.1002/anie.201905003

文献信息

• Synthesis, Characterization, Mechanism of Decomposition, and Antiproliferative Activity of a Class of PEGylated Benzopolysulfanes Structurally Similar to the Natural Product Varacin
  作者：Adaickapillai Mahendran、Angela Vuong、David Aebisher、Yaqiong Gong、Robert Bittman、Gilbert Arthur、Akira Kawamura、Alexander Greer

  DOI：10.1021/jo100870q

  日期：2010.8.20

  Benzopolysulfanes, 4-CH3(OCH2CH2)(3)NHC(O)-C6H4-1,2-S-x (x = 3-7 and 9) were synthesized with a PEG group attached through an amide bond and examined for water solubility, antitumor activity, and propensity to equilibrate and desulfurate. LCMS and HPLC data show the PEG pentasulfane ring structure predominates, and the tri-, tetra-, hexa-, hepta-, and nonasulfanes were present at very low concentrations. The presence of the PEG group improved water solubility by 50-fold compared to the unsubstituted benzopolysulfanes, C6H4Sx (x = 3, 5, and 7), based on intrinsic solubility measurements. Polysulfur linkages in the PEG compounds decomposed in the presence of ethanethiol and hydroxide ion. The PEG pentathiepin desulfurated rapidly, and an S-3 transfer reaction was observed in the presence of norbornene; no S-2 transfer reaction was observed with 2,3-dimethylbutadiene. The antitumor activities of the PEG-substituted benzopolysulfane mixtures were analyzed against four human tumor cell lines PC3 (prostate), DU145 (prostate), MDA-MB-231 (breast), and Jurkat (T-cell leukemia). The PEG-conjugated polysulfanes had IC50 values 1.2-5.8 times lower than the parent "unsubstituted" benzopolysulfanes. Complete cell killing was observed for the PEG polysulfanes at 4 mu M for PC3 and DU145 cells and at 12 mu M for MDA-MB-231 cells. The results suggest that solubilization of the polysulfur linkage is a key parameter to the success of these compounds as drug leads.
• Cell‐Penetrating Dynamic‐Covalent Benzopolysulfane Networks
  作者：Yangyang Cheng、Lili Zong、Javier López‐Andarias、Eline Bartolami、Yasunori Okamoto、Thomas R. Ward、Naomi Sakai、Stefan Matile

  DOI：10.1002/anie.201905003

  日期：2019.7.8

  is a dynamic‐covalent network of extreme sulfur species, including cyclic oligomers, from dimers to heptamers, with up to nineteen sulfurs in the ring. Selection from this unfolding adaptive network then yields the reactivities and selectivities needed to access new uptake pathways. Contrary to other COCs, BPS show high retention on thiol affinity columns. The identification of new modes of cell penetration

  环状寡硫属化合物（COC）有望成为渗透细胞的有前途的系统。明显优于和不同于已报道的二硒代壬二烯和表二硫代二酮哌嗪，我们引入了苯并多硫烷（BPS），它们显示出有效的递送，对内吞作用抑制剂的不敏感性以及与蛋白质一样大的底物的相容性。这种高活性与选择性地对硫醇的高反应性相吻合，超过了二硫化物在张力下的交换速率。其结果是形成了一个动态的共价网络，其中包括从二聚体到七聚体的最高硫物种，包括环状低聚物，环中最多包含19个硫。然后，从这个不断发展的自适应网络中进行选择，即可获得进入新的吸收途径所需的反应性和选择性。与其他COC相反，BPS在硫醇亲和柱上显示出很高的保留率。
• Synthesis and antiproliferative properties of a new ceramide analog of varacin
  作者：Adaickapillai Mahendran、Ashwini A. Ghogare、Robert Bittman、Gilbert Arthur、Alexander Greer

  DOI：10.1016/j.chemphyslip.2015.07.023

  日期：2016.1

  A benzopentasulfane was synthesized in 8 steps with a ceramide attached through an amide bond to the 7-position of the heterocycle structure. The anticancer activity of this synthetic ceramide-benzopolysulfane drug conjugate was analyzed against five human cancer cell lines MDA-MB-231 (breast), DU145 (prostate), MIA PaCa-2 (pancreas), HeLa (cervix), and U251 (glioblastoma). The ceramide-benzopolysulfane conjugate had IC50 values ranging from 10 to >20 mu M with complete cell killing at 12.5 mu M for MDA-MB-231 and 20 mu M for DU145 and HeLa cells. The ceramide-benzopolysulfane conjugate had IC50 values 1.8 and 4.0 times lower than a PEG benzopolysulfane, N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzo[f][1,2,3,4,5]-pentathiepine-7-carboxamide, for MDA-MB-231 and DU145 cells, respectively. The parent "unsubstituted" benzopolysulfane, o-C6H4S5, had IC50 values 4.2 times lower and 2.7 times higher than the ceramide benzopolysulfane for MDA-MB-231 and DU145 cells, respectively. The results indicate that the polysulfur linkage is needed for activity since benzenedithiol, o-C6H4(SH)(2), had IC50 values greater than 30 mu M with little effect on MDA-MB-231 and DU145 cells. Thus, to account for the bioactivity, a bimolecular reaction of cellular thiol with the ceramide benzopolysulfane is a proposed followed by thiozone (S-3) extrusion. (C) 2015 Elsevier Ireland Ltd. All rights reserved.