2,3-dichloro-6-ethyl-5,8-dihydroxy-1,4-naphthoquinone | 610311-09-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2,3-dichloro-6-ethyl-5,8-dihydroxy-1,4-naphthoquinone
• 英文别名: 5,8-dihydroxy-2,3-dichloro-6-ethyl-1,4-naphthoquinone；6,7-dichloro-2-ethyl-5,8-dihydroxy-1,4-naphthoquinone；dichloroethylnaphthazarin
• CAS: 610311-09-6
• 化学式: C₁₂H₈Cl₂O₄
• 分子量: 287.099
• InChiKey: XOMJUKWGTKWWLB-UHFFFAOYSA-N

物化性质

• 沸点：
  501.7±50.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.6
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2,3-dichloro-6-ethyl-5,8-dihydroxy-1,4-naphthoquinone 在 manganese(IV) oxide 、 硫酸 、 铁粉 、 溶剂黄146 作用下， 反应 1.5h， 生成 1,4-Naphthalenedione, 6-ethyl-2,5,8-trihydroxy-
  参考文献：
  名称：

  摘要：

  A series of substituted (poly)hydroxylated naphthazarins (5.8-dihydroxy-1,4-naphthoquinones) were synthesized. In general, (poly) hydroxynaphthazarins exist in organic aprotic solvents as mixtures of tautomeric 1,4-naphthoquinonoid forms (IR data). The ratio of tautomers was determined for the first time. The effects of the nature of substituents and the solvent polarity on the tautomeric equilibrium were qualitatively estimated,

  DOI：

  10.1023/a:1022425121552
• 作为产物：
  描述：

  2,3-二氯马来酸酐 、 2-乙基-1,4-二甲氧基苯 在 三氯化铝 、 sodium chloride 、 盐酸 作用下， 以 水 为溶剂， 反应 12.08h， 以88%的产率得到2,3-dichloro-6-ethyl-5,8-dihydroxy-1,4-naphthoquinone
  参考文献：
  名称：

  Spinazarin and ethylspinazarin, pigments of the sea urchin Scaphechinus mirabilis

  摘要：

  2,3,5,8-四羟基-1,4-萘醌（spinazarin）和6-乙基-2,3,5,8-四羟基-1,4-萘醌（乙基spinazarin）首先从海胆Scaphechinus mirabilis中分离出来。根据光谱数据分析确定了菠那素的结构。提出了乙基螺菌素的制备合成路线。

  DOI：

  10.1007/s11172-007-0122-0

文献信息

• Reaction of Dichloronaphthazarins with Sodium Nitrite as a Route to Natural Pigments Echinamines A and B and Related Aminonaphthazarins
  作者：Nikita Polonik、Sergey Polonik、Vladimir Denisenko、Olga Moiseenko

  DOI：10.1055/s-0030-1260229

  日期：2011.10

  A series of 6,7-disubstituted 2-hydroxy-3-nitronaphthazarins were prepared by treatment of 2,3-dichloronaphthazarins with sodium nitrite. Acid-catalyzed hydrolysis of a mixture of two isomeric 6(7)-ethoxy-7(6)-ethyl-substituted 2-hydroxy-3-nitronaph­thazarins followed by chromatographic separation led to the individually precursors of echinamines A and B. Further reduction of nitroquinones using various reducing agents gave echinamines and related 3-amino-2-hydroxynaphthazarins in good yields.

  一系列6,7-取代的2-羟基-3-硝基萘唑被制备，方法是将2,3-二氯萘唑与亚硝酸钠反应。通过酸催化水解一混合的两个异构体6(7)-乙氧基-7(6)-乙基取代的2-羟基-3-硝基萘唑，随后进行色谱分离，得到了引物独立的艾奇胺A和B。进一步使用各种还原剂对硝基喹酮进行还原，良好产率地得到了艾奇胺及相关的3-氨基-2-羟基萘唑。
• Activity of New Synthetic (2-Chloroethylthio)-1,4-naphthoquinones in Prostate Cancer Cells
  作者：Sergey A. Dyshlovoy、Dmitry N. Pelageev、Lea S. Jakob、Ksenia L. Borisova、Jessica Hauschild、Tobias Busenbender、Moritz Kaune、Ekaterina A. Khmelevskaya、Markus Graefen、Carsten Bokemeyer、Victor Ph. Anufriev、Gunhild von Amsberg

  DOI：10.3390/ph14100949

  日期：——

  Development of resistance to currently available standard therapies in advanced prostate cancer (PCa) emphasizes the need for novel therapeutic options. Here, we report the synthesis of new hybrid molecules consisting of 2-chloroethylthio and 1,4-naphthoquinone pharmacophores and describe their activity in PCa. In screening analyses, the introduction of one 2-chloroethylthio group improved the anticancer properties of 1,4-naphthoquinones, whereas the introduction of a second 2-chloroethylthio moiety rather decreased activity. Two most promising of the synthesized compounds, 30 and 32, were highly active in different human PCa cell lines harboring varying resistance profiles at nanomolar concentrations. The generated data suggest that the compounds are capable of mitochondria targeting, cytotoxic ROS induction, and DNA damage, which resulted in apoptosis presumably executed in a caspase-dependent manner. The substances synergized with the clinically approved PARP inhibitor olaparib and resensitized AR-V7-expressing PCa cells to antiandrogen enzalutamide, as well as to a combination of enzalutamide and an AKT inhibitor. This was at least in part exerted via down-regulation of AR-V7 expression and inhibition of AR signaling. Mild antagonism was observed in combination with platinum- or taxane-based chemotherapy, which was putatively related to treatment-induced activation of p38, JNK1/2, ERK1/2, MEK1/2, and AKT, functioning as potential pro-survival factors. Thus, the synthesized (2-chloroethylthio)-1,4-naphthoquinone derivatives exhibit promising anticancer properties in vitro, suggesting their further development as potential therapeutics for the treatment of castration-resistant PCa.

  目前，晚期前列腺癌（PCa）对现有标准疗法的耐药性的发展强调了新型治疗选择的必要性。在这里，我们报道了2-氯乙基硫和1,4-萘醌药效团组成的新型杂化分子的合成，并描述了它们在PCa中的活性。在筛选分析中，引入一个2-氯乙基硫基团改善了1,4-萘醌的抗癌性能，而引入第二个2-氯乙基硫基团则降低了活性。合成的两个最有前途的化合物30和32，在不同人类PCa细胞系中具有高活性，这些细胞系具有不同的耐药谱，浓度为纳摩尔级。生成的数据表明，这些化合物能够靶向线粒体，诱导细胞毒性ROS和DNA损伤，导致凋亡，可能是以caspase依赖的方式执行的。这些物质与临床批准的PARP抑制剂olaPARib协同作用，并使表达AR-V7的PCa细胞重新对抗雄激素受体拮抗剂恩扎鲁胺以及恩扎鲁胺和AKT抑制剂的联合治疗产生敏感性。这至少部分是通过下调AR-V7表达和抑制AR信号传导来发挥作用的。与铂类或紫杉醇类化疗的联合治疗中观察到轻度的拮抗作用，这可能与治疗引起的p38、JNK1/2、ERK1/2、MEK1/2和AKT的潜在促生存因子的活化有关。因此，合成的（2-氯乙基硫基）-1,4-萘醌衍生物在体外展示了有前途的抗癌性能，建议将其进一步开发为治疗去势抵抗性PCa的潜在治疗药物。
• A simple synthesis of natural spinazarins and their analogues
  作者：Dmitry N. Pelageev、Ksenia L. Borisova、Svetlana M. Kovach、Vyacheslav V. Makhankov、Victor Ph. Anufriev

  DOI：10.1016/j.mencom.2023.02.026

  日期：2023.3

  simple synthesis of spinazarins (2,3-dihydroxy-naphthazarins or 2,3,5,8-tetrahydroxy-1,4-naphtho-quinones) from available 2,3-dichloronaphthazarin derivatives involves replacement of chlorine atoms with azido groups followed by their acidic hydrolysis. The procedure can be used for the preparative synthesis of natural biologically active spinazarins and their analogues.

  从可用的 2,3-二氯萘并衍生物中简单合成 spinazarin（2,3-二羟基-萘并或 2,3,5,8-四羟基-1,4-萘并醌）涉及用叠氮基取代氯原子，然后通过它们的酸性水解。该程序可用于天然生物活性菠菜素及其类似物的制备合成。
• Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity
  作者：Irina Agafonova、Ekaterina Chingizova、Elena Chaikina、Ekaterina Menchinskaya、Sergey Kozlovskiy、Galina Likhatskaya、Yuri Sabutski、Sergey Polonik、Dmitry Aminin、Evgeny Pislyagin

  DOI：10.3390/md22020062

  日期：——

  The MTS cell viability test was used to screen a mini library of natural and synthetic 1,4-naphthoquinone derivatives (1,4-NQs) from marine sources. This screening identified two highly effective compounds, U-443 and U-573, which showed potential in protecting Neuro-2a neuroblastoma cells from the toxic effects of rotenone in an in vitro model of neurotoxicity. The selected 1,4-NQs demonstrated the

  MTS 细胞活力测试用于筛选海洋来源的天然和合成 1,4-萘醌衍生物 (1,4-NQ) 的迷你库。此次筛选确定了两种高效化合物 U-443 和 U-573，它们在体外神经毒性模型中显示出保护 Neuro-2a 神经母细胞瘤细胞免受鱼藤酮毒性作用的潜力。选定的 1,4-NQ 表现出通过降低 Neuro-2a 神经母细胞瘤细胞和 RAW 264.7 巨噬细胞中活性氧 (ROS) 和一氧化氮 (NO) 水平来减少氧化应激的能力，并在小鼠大脑中显示出显着的抗氧化特性匀浆。暴露于神经毒素后，1,4-NQ 可以恢复正常线粒体功能，线粒体膜电位也恢复。此外，在低浓度下，这些化合物被发现可显着降低促炎细胞因子 TNF 和 IL-1β 的水平，并显着抑制 RAW 264.7 巨噬细胞中环氧合酶-2 (COX-2) 的活性。对接研究的结果表明，1,4-NQ 与 COX-2 的活性位点结合，类似于该酶的已知抑制剂
• Synthesis and properties of water-soluble 5,8-dihydroxy-1,4-naphthoquinone thioglucosides structurally related to echinochrome
  作者：S. G. Polonik

  DOI：10.1134/s1070428009100091

  日期：2009.10

  Acetylated hydroxynaphthazarin di- and trithioglucosides structurally related to echinochrome were synthesized. Their deacetylation by the action of sodium methoxide in methanol and the effect of hydroxy groups on this process were studied. Water-soluble echinochrome thioglucosides were synthesized for the first time.