(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
• 1-[4-(2-Dimethylaminoethoxy)phenylcarbonyl]-3,5-Bis(3,4,5-Trimethoxybenzylidene)- 4-Piperidone Hydrochloride and Related Compounds: Potent Cytotoxins Demonstrate Greater Toxicity to Neoplasms than Non- Malignant Cells
  作者：Praveen K. Roayapalley、Jonathan R. Dimmock、Hiroshi Sakagami、Noriyki Okudaira、Rajendra K. Sharma、Umashankar Das

  DOI：10.2174/1573406418666220322154110

  日期：2022.11

  The incidence of cancer has been increasing worldwide. Unfortunately, the drugs used in cancer chemotherapy are toxic to both neoplasms and normal tissues, while many available medications have low potencies. Conjugated α,β-unsaturated ketones differ structurally from contemporary anticancer medications, and some of which have

  To design and synthesize highly potent cytotoxins with far greater toxicity to neoplasms than to non-malignant cells.

  A series of N-acyl-3,5-bis(benzylidene)-4-piperidone hydrochlorides 4a-n were prepared and evaluated against Ca9-22, HSC-2, HSC-3, and HSC-4 squamous cell carcinomas as well as aginst HGF, HPLF, and HPC non-malignant cells. QSAR and western blot analyses were performed.

  The majority of compounds display submicromolar CC50 values towards the neoplasms; the figures for some of the compounds are below 10-7 M. In general, 4a-n have much lower CC50 values than those of melphalan, 5-fluorouracil, and methotrexate, while some compounds are equitoxic with doxorubicin. The compounds are far less toxic to the non-malignant cells, giving rise to substantial selectivity index (SI) figures. A QSAR study revealed that both potency and the SI data were controlled to a large extent by the electronic properties of the substituents in the arylidene aryl rings. Two representative compounds 4f and 4g caused apoptosis in HSC-2 cells.

  The compounds in series 4 are potent cytotoxins displaying tumor-selective toxicity. In particular, 4g with an average CC50 value of 0.04 µM towards four malignant cell lines and a selectivity index of 46.3 is clearly a lead molecule that should be further evaluated.

  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。
• 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.
• C5-curcuminoid-dithiocarbamate based molecular hybrids: synthesis and anti-inflammatory and anti-cancer activity evaluation
  作者：Amit Anthwal、Kundan Singh、M. S. M. Rawat、Amit K. Tyagi、Bharat B. Aggarwal、Diwan S. Rawat

  DOI：10.1039/c4ra03655g

  日期：——

  The C5-curcumin-dithiocarbamate analogues were synthesized in search of new molecules with anti-proliferation potential against cancer cells. These new compounds demonstrated higher anti-proliferation and anti-inflammatory activity against cancer cell lines in comparison to curcumin.

  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。