1-{[2-(4-nitrophenyl)ethyl]amino}-4-propoxy-9H-thioxanthen-9-one | 1351934-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫色烯
• 英文名称: 1-{[2-(4-nitrophenyl)ethyl]amino}-4-propoxy-9H-thioxanthen-9-one
• 英文别名: 1-[2-(4-Nitrophenyl)ethylamino]-4-propoxythioxanthen-9-one
• CAS: 1351934-68-3
• 化学式: C₂₄H₂₂N₂O₄S
• 分子量: 434.516
• InChiKey: OBOLIYWPNGDJDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-硝基苯乙胺 、 1-氯-4-丙氧基硫杂蒽-9-酮 在 copper(l) iodide 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 1-{[2-(4-nitrophenyl)ethyl]amino}-4-propoxy-9H-thioxanthen-9-one
  参考文献：
  名称：

  噻吨酮文库的抗菌活性及其作为外排泵抑制剂的潜力

  摘要：

  外排泵的过度表达是引起多药耐药的原因之一，导致药物无效。这在抗菌素耐药性中起着举足轻重的作用，最显着的泵是 AcrAB-TolC 系统（AcrB 属于耐药性结节分裂家族）和来自主要促进剂超家族的 NorA。在细菌中，这些结构也有利于毒力和适应机制，例如群体感应和生物膜的形成。在这项研究中，描述了作为潜在外排泵抑制剂的噻吨酮库的设计和合成。对噻吨酮衍生物的抗菌活性和外排泵抑制、生物膜形成和群体感应进行了研究。还研究了这些化合物与 P-糖蛋白（P-gp，ABCB1）相互作用的潜力，存在于哺乳动物细胞中的外排泵，以及它们在小鼠成纤维细胞和人 Caco-2 细胞中的细胞毒性。关于实时溴化乙锭积累的结果可能表明潜在的细菌外排泵抑制作用，尚未报道噻吨酮。此外，人体细胞的体外研究表明，Caco-2 细胞中浓度高达 20 µM 时缺乏细胞毒性，一些衍生物也显示出 P-gp 调节的潜力。

  DOI：

  10.3390/ph14060572

文献信息

• Dual inhibitors of P-glycoprotein and tumor cell growth: (Re)discovering thioxanthones
  作者：Andreia Palmeira、M. Helena Vasconcelos、Ana Paiva、Miguel X. Fernandes、Madalena Pinto、Emília Sousa

  DOI：10.1016/j.bcp.2011.10.004

  日期：2012.1

  For many pathologies, there is a crescent effort to design multiple ligands that interact with a wide variety of targets. 1-Aminated thioxanthone derivatives were synthesized and assayed for their in vitro dual activity as antitumor agents and P-glycoprotein (P-gp) inhibitors. The approach was based on molecular hybridization of a thioxanthone scaffold, present in known antitumor drugs, and an amine, described as an important pharmacophoric feature for P-gp inhibition. A rational approach using homology modeling and docking was used, to select the molecules to be synthesized by conventional or microwave-assisted Ullmann C-N cross-coupling reaction. The obtained aminated thioxanthones were highly effective at inhibiting P-gp and/or causing growth inhibition in a chronic myelogenous leukemia cell line, K562. Six of the aminated thioxanthones had GI(50) values in the 1(562 cell line below 10 mu M and 1-[2-(diethylamino)ethyl]amino}-4-propoxy-9H-thioxanthen-9-one (37) had a GI(50) concentration (1.90 mu M) 6-fold lower than doxorubicin (11.89 mu M) in the K562Dox cell line. The best P-gp inhibitor found was 1-[2-(1H-benzimidazol-2-yl)ethanamine]-4-propoxy-9H-thioxanthen-9-one (45), which caused an accumulation rate of rhodamine-123 similar to that caused by verapamil in the K562Dox resistant cell line, and a decrease in ATP consumption by P-gp. At a concentration of 10 mu M, compound 45 caused a decrease of 12.5-fold in the GI(50) value of doxorubicin in the K562Dox cell line, being 2-fold more potent than verapamil. From the overall results, the aminated thioxanthones represent a new class of P-gp inhibitors with improved efficacy in sensitizing a resistant P-gp overexpressing cell line (K562Dox) to doxorubicin. (C) 2011 Elsevier Inc. All rights reserved.
• Antimicrobial Activity of a Library of Thioxanthones and Their Potential as Efflux Pump Inhibitors
  作者：Fernando Durães、Andreia Palmeira、Bárbara Cruz、Joana Freitas-Silva、Nikoletta Szemerédi、Luís Gales、Paulo Martins da Costa、Fernando Remião、Renata Silva、Madalena Pinto、Gabriella Spengler、Emília Sousa

  DOI：10.3390/ph14060572

  日期：——

  design and synthesis of a library of thioxanthones as potential efflux pump inhibitors are described. The thioxanthone derivatives were investigated for their antibacterial activity and inhibition of efflux pumps, biofilm formation, and quorum-sensing. The compounds were also studied for their potential to interact with P-glycoprotein (P-gp, ABCB1), an efflux pump present in mammalian cells, and for

  外排泵的过度表达是引起多药耐药的原因之一，导致药物无效。这在抗菌素耐药性中起着举足轻重的作用，最显着的泵是 AcrAB-TolC 系统（AcrB 属于耐药性结节分裂家族）和来自主要促进剂超家族的 NorA。在细菌中，这些结构也有利于毒力和适应机制，例如群体感应和生物膜的形成。在这项研究中，描述了作为潜在外排泵抑制剂的噻吨酮库的设计和合成。对噻吨酮衍生物的抗菌活性和外排泵抑制、生物膜形成和群体感应进行了研究。还研究了这些化合物与 P-糖蛋白（P-gp，ABCB1）相互作用的潜力，存在于哺乳动物细胞中的外排泵，以及它们在小鼠成纤维细胞和人 Caco-2 细胞中的细胞毒性。关于实时溴化乙锭积累的结果可能表明潜在的细菌外排泵抑制作用，尚未报道噻吨酮。此外，人体细胞的体外研究表明，Caco-2 细胞中浓度高达 20 µM 时缺乏细胞毒性，一些衍生物也显示出 P-gp 调节的潜力。