(3E,5E)-3,5-bis(3-fluorobenzylidene)piperidin-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3E,5E)-3,5-bis(3-fluorobenzylidene)piperidin-4-one
• 英文别名: (3E,5E)-3,5-bis[(3-fluorophenyl)methylidene]piperidin-4-one
• 化学式: C₁₉H₁₅F₂NO
• 分子量: 311.331
• InChiKey: VCWPQHLVPFODON-BGPOSVGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3E,5E)-3,5-bis(3-fluorobenzylidene)piperidin-4-one 在 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 2-((3E,5E)-3,5-bis(3-fluorobenzylidene)-4-oxopiperidin-1-yl)-2-oxoethyl morpholine-4-carbodithioate
  参考文献：
  名称：

  C5-curcuminoid-dithiocarbamate based molecular hybrids: synthesis and anti-inflammatory and anti-cancer activity evaluation

  摘要：

  C5-姜黄二硫代氨基甲酸盐类似物是为寻找具有抗癌细胞增殖潜力的新分子而合成的。这些新化合物与姜黄相比，在抗癌细胞系中表现出更高的抗增殖和抗炎活性。

  DOI：

  10.1039/c4ra03655g
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 、 3-氟苯甲醛 在 盐酸 、 溶剂黄146 作用下， 反应 24.0h， 生成 (3E,5E)-3,5-bis(3-fluorobenzylidene)piperidin-4-one
  参考文献：
  名称：

  1-[4-(2-二甲氨基乙氧基)苯基羰基]-3,5-双(3,4,5-三甲氧基亚苄基)-4-哌啶酮盐酸盐及相关化合物：强效细胞毒素对肿瘤的毒性比非恶性细胞更大

  摘要：

  背景：癌症发病率正在全球范围内增加。不幸的是，用于癌症化疗的药物对肿瘤和正常组织都有毒性，而许多可用药物的效力较低。共轭α，β-不饱和酮在结构上与现代抗癌药物不同，其中一些具有... 目标：设计和合成高效的细胞毒素，对肿瘤细胞的毒性远高于非恶性细胞。 方法：制备了一系列N-酰基-3,5-双(苄亚甲基)-4-哌啶酮盐酸盐4a-n，并对Ca9-22、HSC-2、HSC-3和HSC-4鳞状细胞癌以及HGF、HPLF和HPC非恶性细胞进行了评估。进行了QSAR和Western blot分析。 结果：大多数化合物在肿瘤细胞上显示亚微摩尔水平的CC50值；其中一些化合物的数值低于10-7 M。总体而言，4a-n的CC50值远低于甲氧氨基甲烷、5-氟尿嘧啶和甲氨蝶呤，而一些化合物与多柔比星的毒性相当。这些化合物对非恶性细胞的毒性远低于肿瘤细胞，产生了相当大的选择性指数（SI）值。QSAR研究表明，芳基亚甲基环上取代基的电子性质在很大程度上控制了效力和SI数据。两个代表性化合物4f和4g在HSC-2细胞中引起了凋亡。 结论：系列4中的化合物是具有肿瘤选择性毒性的有效细胞毒素。特别是4g，其对四种恶性细胞系的平均CC50值为0.04 µM，选择性指数为46.3，显然是一个应该进一步评估的领头化合物。

  DOI：

  10.2174/1573406418666220322154110

文献信息

• Novel hybrid molecules of 3,5-bis(benzylidene)-4-piperidones and dichloroacetic acid which demonstrate potent tumour-selective cytotoxicity
  作者：Mohammad Hossain、Swagatika Das、Umashankar Das、Alireza Doroudi、Jianfeng Zhu、Jonathan R. Dimmock

  DOI：10.1016/j.bmcl.2019.126878

  日期：2020.2

  A novel class of hybrid molecules 2a-o was designed as candidate antineoplastic agents from dichloroacetic acid which is a known inhibitor of pyruvate dehydrogenase kinase and a number of cytotoxic 3,5-bis(benzylidene)-4-piperidones 1. In general these new hybrid molecules are potent cytotoxins towards human HCT116 colon cancer cells. A number of lead molecules emerged having the IC50 values in the

  从二氯乙酸中设计了一类新型的杂合分子2a-o作为候选抗肿瘤药，二氯乙酸是丙酮酸脱氢酶激酶和许多具有细胞毒性的3,5-双（亚苄基）-4-哌啶酮1的抑制剂。杂合分子是针对人HCT116结肠癌细胞的有效细胞毒素。出现了许多铅分子，其IC50值在两位数纳摩尔范围内。这些化合物中的大多数对人CRL1790非恶性结肠细胞的毒性较小，因此，大多数化合物的选择性指数（SI）值很高。在2c-g，m，n的情况下，SI值超过100。与参考药物5-FU相比，化合物2g，2j，2m和2n的效价高100倍以上。定量的构效关系表明，随着Hammettσ和Taftσ*值的增加，系列2中化合物的效能也增加。代表性化合物2c的X射线晶体学揭示了可能影响细胞毒性的各种结构特征。几种代表性化合物降低了HCT116细胞中的线粒体膜电位，并增加了活性氧的产生。在改变细胞周期不同阶段中的细胞百分比方面，注意到最小的作用。已经为模拟开发
• Fluorinated and N-Acryloyl-Modified 3,5-Di[(E)-benzylidene]piperidin-4-one Curcuminoids for the Treatment of Pancreatic Carcinoma
  作者：Hindole Ghosh、Sangita Bhattacharyya、Rainer Schobert、Prasad Dandawate、Bernhard Biersack

  DOI：10.3390/pharmaceutics15071921

  日期：——

  Pancreatic carcinoma is a cancer disease with high mortality. Thus, new and efficient treatments for this disease are badly needed. Curcumin has previously shown promising effects in pancreatic cancer patients; however, this natural compound suffers from inadequate efficacy and bioavailability, preventing its clinical approval. The synthetic curcuminoid EF24 was developed with activities superior to curcumin against various cancer types. In this study, a series of analogs of EF24 were investigated for anticancer effects on pancreatic carcinoma models. A distinct activity boost was achieved by straightforward N-acrylation of EF24 analogs, in particular, of compounds bearing 3-fluoro-4-methoxybenzylidene, 3,4-difluorobenzylidene, and 4-trifluoromethylbenzylidene moieties, while no improvement was seen for N-acryloyl-modified EF24. Apoptosis induction and suppression of phospho-STAT3 levels were determined, the latter corroborated by docking of active curcuminoids into STAT3. Hence, promising new clues for the development of efficient and superior curcuminoids as valuable treatment options for one of the most lethal cancer diseases were discovered in this study.

  胰腺癌是一种死亡率很高的癌症疾病。因此，亟需新的高效疗法来治疗这种疾病。姜黄素曾在胰腺癌患者中显示出良好的疗效，但由于这种天然化合物的疗效和生物利用度不足，无法获得临床批准。合成姜黄素 EF24 被开发出来，其对各种癌症类型的活性优于姜黄素。在这项研究中，我们研究了 EF24 的一系列类似物对胰腺癌模型的抗癌作用。通过对 EF24 类似物，特别是含有 3-氟-4-甲氧基亚苄基、3,4-二氟亚苄基和 4-三氟甲基亚苄基的化合物进行直接 N-丙烯酰化，可以明显提高其活性，而 N-丙烯酰改性的 EF24 则没有提高活性。凋亡诱导和磷酸化 STAT3 水平的抑制作用已经确定，后者通过活性姜黄素与 STAT3 的对接得到了证实。因此，本研究发现了开发高效、优质姜黄素的新线索，可作为治疗最致命癌症之一的重要方法。
• Synthesis and anti-tumor activity of EF24 analogues as IKKβ inhibitors
  作者：Rong Jin、Qiuxiang Chen、Song Yao、Encheng Bai、Weitao Fu、Ledan Wang、Jiabing Wang、Xiaojing Du、Tao Wei、Haineng Xu、Chengxi Jiang、Peihong Qiu、Jianzhang Wu、Wulan Li、Guang Liang

  DOI：10.1016/j.ejmech.2017.11.077

  日期：2018.1

  EF24 is an IKK beta inhibitor (IC50: 72 mu M) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKK beta were designed and synthesized. Several IKK beta inhibitors with better activities than EF24 were screened out and B3 showed best IKK beta inhibitory (IC50: 6.6 mu M). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-kappa B signal pathway by inhibiting IKK beta phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKK beta-NF-kappa B signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKK beta inhibitor as anti-tumor precursor. (C) 2017 Published by Elsevier Masson SAS.
• Discovery of novel cage-like heterocyclic hybrids as anti-inflammatory agents through the inhibition of nitrite, PGE2 and TNF-α
  作者：Raju Suresh Kumar、Paulrayer Antonisamy、Abdulrahman I. Almansour、Natarajan Arumugam、Dhaifallah M. Al-thamili、Raju Ranjith Kumar、Ha-Rim Kim、Kang-Beom Kwon

  DOI：10.1016/j.bioorg.2019.103180

  日期：2019.10

  Novel cage-like indolizine-acenaphthene-pyridinone heterocyclic hybrids were synthesized in good yields through [bmim]Br mediated tandem 1,3-dipolar cycloaddition-annulation sequence. The anti-inflammatory activity of these hybrids was performed using carrageenan-induced hind paw oedema, croton oil-induced ear oedema and cotton pellet-induced granuloma models. Four of these cage-like heterocyclic hybrids viz. 4b, 4d, 4e and 4j showed substantial anti-inflammatory activities against acute and chronic inflammatory models and also showed significant inhibition of PGE(2), TNF-alpha, and nitrite levels in carrageenan-induced hind paw oedema.