3'-chloro-3-hydroxy-7-methoxy-2,2'-binaphthalenyl-1,4,1',4'-tetraone | 405264-32-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3'-chloro-3-hydroxy-7-methoxy-2,2'-binaphthalenyl-1,4,1',4'-tetraone
• CAS: 405264-32-6
• 化学式: C₂₁H₁₁ClO₆
• 分子量: 394.768
• InChiKey: BVUMTUQJCBRNFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  28.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  97.74
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3'-chloro-3-hydroxy-7-methoxy-2,2'-binaphthalenyl-1,4,1',4'-tetraone 在 N,N-二甲基甲酰胺 草酰氯 、 氨 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 3'-amino-3-chloro-7-methoxy-2,2'-binaphthalenyl-1,4,1',4'-tetraone
  参考文献：
  名称：

  甲氧基位置对涉及3,3'-Dichloro-2,2'-联萘醌的氨取代反应区域选择性的影响

  摘要：

  制备了一系列甲氧基取代的3,3'-二氯-2,2'-联萘醌2，并评估了氨取代反应中的区域选择性。联苯醌2b在未取代的氯萘醌单元上进行了区域特异性胺化，而异构联苯醌2c产生了中等的区域选择性（85:15）。然而，联苯醌2d没有显示出区域选择性的水平，表明甲氧基的位置会影响区域化学。联醌5中的分子内氢键改变了区域选择性。半经验计算表明，在进行优先取代的氯化碳上，LUMO系数相对较大。

  DOI：

  10.1021/jo049713g
• 作为产物：
  描述：

  碘正离子,苯基-,3,4-二氢-1,3,4-三羰基-2(1H)-萘自由基负离子 在 三甲基氯硅烷 、 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 144.5h， 生成 3'-chloro-3-hydroxy-7-methoxy-2,2'-binaphthalenyl-1,4,1',4'-tetraone
  参考文献：
  名称：

  Regiocontrolled synthesis and HIV inhibitory activity of unsymmetrical binaphthoquinone and trimeric naphthoquinone derivatives of conocurvone

  摘要：

  Unsymmetrical biquinone and trimeric quinone derivatives were synthesized using halotriflate-biselectrophilic naphthoquinones through stepwise regioselective quinone substitution chemistry and evaluated for their ability to inhibit the cytopathogenic effects of HIV-1 using an MTT colorimetric assay. Compounds were also screened for their ability to inhibit the activity of HIV-1 integrase in vitro. Pyranylated trimeric quinones and biquinones exhibited both antiviral activity and integrase inhibitory activity. Conocurvone 1 and trimeric quinone 21 were the most potent HIV integrase inhibitors in the series. All of the biquinones showed HIV inhibitory activity. Simple methoxy substituted biquinones did not inhibit HIV-1 integrase. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2006.04.034

文献信息

• Regiocontrolled Synthesis of the Trimeric Quinone Framework of Conocurvone
  作者：Ashkan Emadi、John S. Harwood、Sahar Kohanim、Kenneth W. Stagliano

  DOI：10.1021/ol010272m

  日期：2002.2.1

  conocurvone is crucial for its potent anti-HIV activity. A new synthesis of trimeric quinones based on stepwise substitution of the halogens in 2,3-dihaloquinones by hydroxyquinone anions is described. Chlorinated biquinones are key intermediates that undergo regiospecific substitution reactions to yield trimeric quinone monomethyl ethers.

  [反应：见正文]香豆酮的三聚体醌构架对其有效的抗HIV活性至关重要。描述了一种新的合成三聚体醌的方法，该方法基于逐步用羟基醌阴离子取代2,3-二卤代醌中的卤素。氯化联苯醌是关键的中间体，会进行区域特异性取代反应以生成三聚体醌单甲醚。
• Hydroxylated Dimeric Naphthoquinones Increase the Generation of Reactive Oxygen Species, Induce Apoptosis of Acute Myeloid Leukemia Cells and Are Not Substrates of the Multidrug Resistance Proteins ABCB1 and ABCG2
  作者：Rena Lapidus、Brandon Carter-Cooper、Mariola Sadowska、Eun Choi、Omasiri Wonodi、Nidal Muvarak、Karthika Natarajan、Lakshmi Pidugu、Anil Jaiswal、Eric Toth、Feyruz Rassool、Arash Etemadi、Edward Sausville、Maria Baer、Ashkan Emadi

  DOI：10.3390/ph9010004

  日期：——

  Selective targeting of the oxidative state, which is a tightly balanced fundamental cellular property, is an attractive strategy for developing novel anti-leukemic chemotherapeutics with potential applications in the treatment of acute myeloid leukemia (AML), a molecularly heterogeneous disease. Dimeric naphthoquinones (BiQs) with the ability to undergo redox cycling and to generate reactive oxygen species (ROS) in cancer cells are a novel class of compounds with unique characteristics that make them excellent candidates to be tested against AML cells. We evaluated the effect of two BiQ analogues and one monomeric naphthoquinone in AML cell lines and primary cells from patients. All compounds possess one halogen and one hydroxyl group on the quinone cores. Dimeric, but not monomeric, naphthoquinones demonstrated significant anti-AML activity in the cell lines and primary cells from patients with favorable therapeutic index compared to normal hematopoietic cells. BiQ-1 effectively inhibited clonogenicity and induced apoptosis as measured by Western blotting and Annexin V staining and mitochondrial membrane depolarization by flow cytometry. BiQ-1 significantly enhances intracellular ROS levels in AML cells and upregulates expression of key anti-oxidant protein, Nrf2. Notably, systemic exposure to BiQ-1 was well tolerated in mice. In conclusion, we propose that BiQ-induced therapeutic augmentation of ROS in AML cells with dysregulation of antioxidants kill leukemic cells while normal cells remain relatively intact. Further studies are warranted to better understand this class of potential chemotherapeutics.

  氧化态是一种紧密平衡的基本细胞特性，选择性靶向氧化态是开发新型抗白血病化疗药物的一种有吸引力的策略，在治疗急性髓性白血病（AML）这种分子异质性疾病方面具有潜在应用。二聚萘醌 (BiQ) 能够进行氧化还原循环并在癌细胞中产生活性氧 (ROS)，是一类具有独特特性的新型化合物，使其成为针对 AML 细胞进行测试的绝佳候选物。我们评估了两种 BiQ 类似物和一种单体萘醌对 AML 细胞系和患者原代细胞的作用。所有化合物在醌核上都具有 1 个卤素和 1 个羟基。与正常造血细胞相比，二聚体而非单体萘醌在治疗指数良好的患者的细胞系和原代细胞中表现出显着的抗 AML 活性。通过蛋白质印迹和膜联蛋白 V 染色以及通过流式细胞术测定线粒体膜去极化来测量，BiQ-1 有效抑制克隆形成并诱导细胞凋亡。 BiQ-1 显着增强 AML 细胞中的细胞内 ROS 水平，并上调关键抗氧化蛋白 Nrf2 的表达。值得注意的是，小鼠对 BiQ-1 的全身暴露具有良好的耐受性。总之，我们提出，BiQ 诱导的 AML 细胞中 ROS 的治疗性增强以及抗氧化剂失调可杀死白血病细胞，而正常细胞则保持相对完整。需要进一步研究以更好地了解此类潜在化疗药物。
• Regiocontrolled synthesis and HIV inhibitory activity of unsymmetrical binaphthoquinone and trimeric naphthoquinone derivatives of conocurvone
  作者：Kenneth W. Stagliano、Ashkan Emadi、Zhenhai Lu、Helena C. Malinakova、Barry Twenter、Min Yu、Louis E. Holland、Amanda M. Rom、John S. Harwood、Ronak Amin、Allison A. Johnson、Yves Pommier

  DOI：10.1016/j.bmc.2006.04.034

  日期：2006.8

  Unsymmetrical biquinone and trimeric quinone derivatives were synthesized using halotriflate-biselectrophilic naphthoquinones through stepwise regioselective quinone substitution chemistry and evaluated for their ability to inhibit the cytopathogenic effects of HIV-1 using an MTT colorimetric assay. Compounds were also screened for their ability to inhibit the activity of HIV-1 integrase in vitro. Pyranylated trimeric quinones and biquinones exhibited both antiviral activity and integrase inhibitory activity. Conocurvone 1 and trimeric quinone 21 were the most potent HIV integrase inhibitors in the series. All of the biquinones showed HIV inhibitory activity. Simple methoxy substituted biquinones did not inhibit HIV-1 integrase. Published by Elsevier Ltd.
• Effect of Methoxyl Group Position on the Regioselectivity of Ammonia Substitution Reactions Involving 3,3‘-Dichloro-2,2‘-binaphthoquinones
  作者：Kenneth W. Stagliano、Zhenhai Lu、Ashkan Emadi、John S. Harwood、Cynthia A. Harwood

  DOI：10.1021/jo049713g

  日期：2004.7.1

  3‘-dichloro-2,2‘-binaphthoquinones 2 were prepared and evaluated for regioselectivity in ammonia substitution reactions. Biquinone 2b underwent regiospecific amination at the unsubstituted chloronaphthoquinone unit whereas the isomeric biquinone, 2c, produced moderate regioselectivity (85:15). Biquinone 2d, however, showed no level of regioselectivity demonstrating that the position of the methoxyl group influences

  制备了一系列甲氧基取代的3,3'-二氯-2,2'-联萘醌2，并评估了氨取代反应中的区域选择性。联苯醌2b在未取代的氯萘醌单元上进行了区域特异性胺化，而异构联苯醌2c产生了中等的区域选择性（85:15）。然而，联苯醌2d没有显示出区域选择性的水平，表明甲氧基的位置会影响区域化学。联醌5中的分子内氢键改变了区域选择性。半经验计算表明，在进行优先取代的氯化碳上，LUMO系数相对较大。