2,6-bis(2-fluorobenzylidene)cyclohexanone | 404917-39-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 2,6-bis(2-fluorobenzylidene)cyclohexanone
• 英文别名: 2,6-Bis(2-fluorobenzylidene)-cyclohexanone；2,6-bis[(2-fluorophenyl)methylidene]cyclohexan-1-one
• CAS: 404917-39-1
• 化学式: C₂₀H₁₆F₂O
• mdl: MFCD00395502
• 分子量: 310.343
• InChiKey: WIDDWATUDMOWCU-UHFFFAOYSA-N

物化性质

• 熔点：
  198-201 °C
• 沸点：
  466.9±45.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,6-bis(2-fluorobenzylidene)cyclohexanone 、 N-叔丁氧羰基-4-哌啶酮 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 144.0h， 以71%的产率得到2-(tert-butoxycarbonyl)-4a-hydroxy-5-(2-fluorobenzylidene)-9-(2-fluorophenyl)-1,2,3,4,4a,5,6,7,8,9,9a-decahydro-2-azaxanthene
  参考文献：
  名称：

  Nitrogen-containing 1,5-diketones based on N-Boc-piperidin-4-one, synthesis, intramolecular cyclization, and reaction with o-phenylenediamine

  摘要：

  Reactions of N-Boc-piperidin-4-one with aromatic aldehydes afforded nitrogen-containing 1,5-diketones in the form of products of intramolecular aldol cyclization, like aza derivatives of tricyclo[7.3.1.0(2,7)]-tridecanone system underlying naturally occurring limonoids. With o-phenylenediamine they enter into a domino-reaction leading to the formation of hydrobenzimidazo[2,1-e]acridine structure. N-Boc-piperidin-4-one in Michael reaction with diarylidenecyclohexanones forms 1,5-diketones undergoing cyclization into hydroxypyran structure.

  DOI：

  10.1134/s107042801511007x
• 作为产物：
  描述：

  环己酮 、 2-氟苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 以80%的产率得到2,6-bis(2-fluorobenzylidene)cyclohexanone
  参考文献：
  名称：

  3,5-双（2-氟苄叉）-4-哌啶酮诱导活性氧介导的A549细胞凋亡

  摘要：

  芳环的邻位上存在取代基有助于增强生物活性，从而突出了所谓的邻位效应。在本文中，我们合成了六个带有氟基团的单羰基姜黄素类似物，这些类似物赋予某些药物多种特性。然后，通过MTT分析评估针对A549和NCI-H460细胞的细胞毒性。结果表明，相对于姜黄素对A549细胞而言，1d表面上是一种重要的先导化合物，显示出几乎13倍的细胞毒性。更重要的是1d姜黄素比姜黄素更稳定，吸收更大，这可能与其姜黄素的细胞毒性，凋亡活性和活性氧的产生有关。活性氧的产生与氧化还原缓冲系统中的崩解有关，并随后引起脂质过氧化，线粒体膜电位的崩溃并最终导致细胞凋亡。这些数据表明邻位作用和将氟引入药物分子是提高单羰基姜黄素类似物的抗癌活性的成功策略。

  DOI：

  10.1007/s00044-017-2056-x

文献信息

• Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes
  作者：Ibrahim Jantan、Syed Nasir Abbas Bukhari、Nordin Haji Lajis、Faridah Abas、Lam Kok Wai、Malina Jasamai

  DOI：10.1111/j.2042-7158.2011.01423.x

  日期：2012.2.6

  A series of 43 curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on the chemiluminescence and chemotactic activity of phagocytes in vitro.

  The effects of the compounds on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) were evaluated using a luminol-based chemiluminescence assay and their effect on chemotactic migration of PMNs was investigated using the Boyden chamber technique.

  Compounds 6, 17, 25 and 30 exhibited significant inhibitory activity on the oxidative burst of PMNs. The presence of methoxy groups at positions 2 and 5, and methoxylation and fluorination at positions 4 and 2 of both phenyl rings, respectively, may contribute significantly to their reactive oxygen species inhibition activity. Compounds 7, 17, 18, 24 and 32 showed strong inhibition of the chemotaxis migration of PMNs. Chlorination at various positions of both phenyl rings of cyclohexanone diarylpentanoid resulted in compounds with potent inhibitory effects on PMN migration.

  The results suggest that some of these diarylpentanoid analogues are able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.

  摘要 目的 合成了一系列43个姜黄素二芳基戊酮类似物，并评估它们对体外吞噬细胞化学发光和趋化活性的抑制作用。 方法 使用基于流明的化学发光测定法评估化合物对人全血和分离的人多形核白细胞（PMNs）呼吸爆发的影响，并利用Boyden室技术研究它们对PMNs趋化迁移的影响。 主要发现 化合物6、17、25和30在PMNs的氧化爆发上表现出显著的抑制活性。在两个苯环的2和5位置有甲氧基基团，以及在4和2位置分别有甲氧化和氟化基团的存在，可能会显著促进它们对活性氧化物种的抑制活性。化合物7、17、18、24和32显示出对PMNs趋化迁移的强烈抑制作用。在环己酮二芳基戊酮类似物的两个苯环的不同位置进行氯化，导致化合物对PMN迁移具有强效抑制作用。 结论 结果表明，这些二芳基戊酮类似物中的一些能够调节吞噬细胞的先天免疫反应的不同步骤，强调它们作为新的免疫调节剂来源的潜力。
• Highly Selective Claisen–Schmidt Condensation Catalyzed by Silica Chloride Under Solvent-Free Reaction Conditions
  作者：Hassan Hazarkhani、Pradeep Kumar、Kadam Sachin Kondiram、Ikhlas M. Shafi Gadwal

  DOI：10.1080/00397910903340637

  日期：2010.8.31

  Silica chloride serves as a useful catalyst in the cross-aldol condensation, leading to the synthesis of a wide variety of bisarylidene cycloalkanones and chalcones. The catalyst showed high selectivity; self-condensation of ketones was not observed.
• Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway
  作者：Pay-Chin Leow、Priti Bahety、Choon Pei Boon、Chong Yew Lee、Kheng Lin Tan、Tianming Yang、Pui-Lai Rachel Ee

  DOI：10.1016/j.ejmech.2013.10.073

  日期：2014.1

  Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/beta-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of beta-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than la (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Anti-inflammatory activity of ortho-trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives in vitro and in vivo
  作者：Ziqing Wang、Wenwen Mu、Pengxiao Li、Guoyun Liu、Jie Yang

  DOI：10.1016/j.ejps.2021.105756

  日期：2021.5
• 3,5-Bis(2-fluorobenzylidene)-4-piperidone induce reactive oxygen species-mediated apoptosis in A549 cells
  作者：Guo-Yun Liu、Cong-Cong Jia、Pu-Ren Han、Jie Yang

  DOI：10.1007/s00044-017-2056-x

  日期：2018.1

  almost 13-fold cytotoxicity relative to curcumin against A549 cells. More importantly, 1d was more stable and more massive uptake than curcumin, which may be relationship to their cytotoxicity, apoptotic acitivity and reactive oxygen species generation. The generation of reactive oxygen species is associated with falling apart in the redox buffering system, and subsequently induces lipid peroxidation

  芳环的邻位上存在取代基有助于增强生物活性，从而突出了所谓的邻位效应。在本文中，我们合成了六个带有氟基团的单羰基姜黄素类似物，这些类似物赋予某些药物多种特性。然后，通过MTT分析评估针对A549和NCI-H460细胞的细胞毒性。结果表明，相对于姜黄素对A549细胞而言，1d表面上是一种重要的先导化合物，显示出几乎13倍的细胞毒性。更重要的是1d姜黄素比姜黄素更稳定，吸收更大，这可能与其姜黄素的细胞毒性，凋亡活性和活性氧的产生有关。活性氧的产生与氧化还原缓冲系统中的崩解有关，并随后引起脂质过氧化，线粒体膜电位的崩溃并最终导致细胞凋亡。这些数据表明邻位作用和将氟引入药物分子是提高单羰基姜黄素类似物的抗癌活性的成功策略。