E-2-[3-(3,4-dichlorophenyl)-1-oxo-2-propenyl]-3-methylquinoxaline-1,4-dioxide | 1172616-42-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: E-2-[3-(3,4-dichlorophenyl)-1-oxo-2-propenyl]-3-methylquinoxaline-1,4-dioxide
• 英文别名: 2-[3-(3,4-dichlorophenyl)-2-propenoyl]-3-methylquinoxaline-1,4-dioxide；(E)-3-(3,4-dichlorophenyl)-1-(3-methyl-4-oxido-1-oxoquinoxalin-1-ium-2-yl)prop-2-en-1-one
• CAS: 1172616-42-0
• 化学式: C₁₈H₁₂Cl₂N₂O₃
• 分子量: 375.211
• InChiKey: XAHAWDKBHCYEEK-VQHVLOKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  63.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二氯苯甲醛 、 乙酰甲喹 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 0.17h， 生成 E-2-[3-(3,4-dichlorophenyl)-1-oxo-2-propenyl]-3-methylquinoxaline-1,4-dioxide
  参考文献：
  名称：

  2-(3-ARYLACRYLOYL)-3-甲基喹喔啉 1,4-二氧化物作为潜在的低氧选择性细胞毒素

  摘要：

  报道了一系列 2-(3-arylacryloyl)-3-methylquinoxaline 1,4dioxides 的合成。这些化合物的体外细胞毒活性通过 MTT 测定在 B16 鼠黑色素瘤和 L1210 鼠白血病细胞系中进行评估。发现二氯类似物是最具细胞毒性的，并且比喹喔啉对照的活性高> 30 倍（IC 50 分别为 2 与 LI210 中的 67 μM）。这些结果表明含有两个生物活性部分的化合物可以开发为低氧选择性细胞毒素。介绍 肿瘤缺氧是由于脉管系统效率低下导致向肿瘤细胞输送氧气不足而引起的一种病症。缺氧似乎是实体瘤中细胞的一种常见且独特的特性，因此已成为治疗干预的目标。生物还原性前药，在缺氧条件下被激活，已经开发出选择性地将细胞毒性部分递送至肿瘤块。这些例子包括 N-氧化物，如苯并三嗪-二-V-氧化物替拉扎明，它在与顺铂联合的 III 期临床试验中显示出显着的活性。提出的细胞毒性机

  DOI：

  10.1515/hc.2008.14.5.385

文献信息

• 2-(3-ARYLACRYLOYL)-3-METHYLQUINOXALINE 1,4-DIOXIDES AS POTENTIAL HYPOXIC SELECTIVE CYTOTOXINS
  作者：Kristin Dittenhafer、Umashankar Das、Brent L. Younglove、Hilary Mackay、Toni Brown、Jonathan R. Dimmock,、Moses Lee、Hari Pati

  DOI：10.1515/hc.2008.14.5.385

  日期：2008.1

  with tirapazamine, and additionally by direct interaction with DNA or DNA-related biomolecules. We report herein the synthesis and cytotoxicity of a series of bioactive hybrid compounds 2a-I containing a quinoxaline 1,4-dioxide motif and an acryloyl group. These compounds should readily diffuse into hypoxic tumor tissue and, via a bioreductive mechanism, promote oxidative DNA cleavage. Subsequently,

  报道了一系列 2-(3-arylacryloyl)-3-methylquinoxaline 1,4dioxides 的合成。这些化合物的体外细胞毒活性通过 MTT 测定在 B16 鼠黑色素瘤和 L1210 鼠白血病细胞系中进行评估。发现二氯类似物是最具细胞毒性的，并且比喹喔啉对照的活性高> 30 倍（IC 50 分别为 2 与 LI210 中的 67 μM）。这些结果表明含有两个生物活性部分的化合物可以开发为低氧选择性细胞毒素。介绍 肿瘤缺氧是由于脉管系统效率低下导致向肿瘤细胞输送氧气不足而引起的一种病症。缺氧似乎是实体瘤中细胞的一种常见且独特的特性，因此已成为治疗干预的目标。生物还原性前药，在缺氧条件下被激活，已经开发出选择性地将细胞毒性部分递送至肿瘤块。这些例子包括 N-氧化物，如苯并三嗪-二-V-氧化物替拉扎明，它在与顺铂联合的 III 期临床试验中显示出显着的活性。提出的细胞毒性机
• 2-(3-Aryl-2-propenoyl)-3-methylquinoxaline-1,4-dioxides: A novel cluster of tumor-specific cytotoxins which reverse multidrug resistance
  作者：Umashankar Das、Hari N. Pati、Atulya K. Panda、Erik De Clercq、Jan Balzarini、Joseph Molnár、Zoltán Baráth、Imre Ocsovszki、Masami Kawase、Li Zhou、Hiroshi Sakagami、Jonathan R. Dimmock

  DOI：10.1016/j.bmc.2009.04.021

  日期：2009.6

  A series of 2-(3-aryl-2-propenoyl)-3-methylquinoxaline-1,4-dioxides 3a-1 were prepared by condensation of various aryl aldehydes with 2-acetyl-3-methylquinoxaline-1,4-dioxide 2. These compounds inhibit the growth of human Molt 4/C8 and CEM T-lymphocytes and the IC50 values are mainly in the 5-30 mu M range. The quinoxaline 1,4-dioxide 3j inhibited the growth of 58 human tumor cell lines, particularly leukemic and breast cancer neoplasms. All of the compounds 3a-1 reversed the multidrug resistance (MDR) properties of murine L-5178Y leukemic cells which were transfected with the human MDR1 gene. The MDR-reversing effect may be due to the conjugated p-electron system forming a weak electron charge transfer complex with the P-glycoprotein-mediated efflux pump. The compounds in series 2 and 3 were assessed against HL-60, HSC-2, HSC-3 and HSC-4 malignant cells as well as HGF, HPC and HPLF normal cell lines which revealed that the majority of the compounds displayed a greater toxicity to neoplastic than normal cells. Various ways in which the project may be expanded are presented. (C) 2009 Elsevier Ltd. All rights reserved.
• E-2-[3-(3,4-Dichlorophenyl)-1-oxo-2-propenyl]-3-methylquinoxaline-1,4-dioxide: A lead antitubercular agent which alters mitochondrial respiration in rat liver
  作者：Umashankar Das、Swagatika Das、Brian Bandy、Dennis K.J. Gorecki、Jonathan R. Dimmock

  DOI：10.1016/j.ejmech.2010.07.030

  日期：2010.10

  A series of 2-(3-aryl-1-oxo-2-propenyl)-3-methylquinoxaline-1,4-dioxides 1a-1 and 2-acetyl-3-methyl-quinoxaline-1,4-dioxide 2 were evaluated against Mycobacterium tuberculosis H(37)Rv. With the exception of the 4-nitro analog 1k, significant antitubercular potencies were observed in series 1 and 2 which have IC(50) values in the range of 1-23 mu M Negative correlations were noted between the IC(50) values of 1a-j, 1 towards M tuberculosis and both the sigma and pi constants of the substituents in the benzylidene aryl ring. In particular, 1h emerged as a lead compound having IC(50) and IC(90) figures of 1.03 mu M and 1 53 mu M, respectively. This molecule affected respiration in rat liver mitochondria which is likely one way that 1h and the bioactive analogs exert their antitubercular properties. The quinoxaline 2, which lacks an alpha,beta-unsaturated group, has no effect on mitochondrial respiration using concentrations which inhibit the growth of M. tuberculosis. (C) 2010 Elsevier Masson SAS All rights reserved.