(3E,5E)-3,5-bis(2,6-difluorobenzylidene)piperidin-4-one | 1431524-76-3

• 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(2,6-difluorobenzylidene)piperidin-4-one
• 英文别名: (3E,5E)-3,5-bis[(2,6-difluorophenyl)methylidene]piperidin-4-one
• CAS: 1431524-76-3
• 化学式: C₁₉H₁₃F₄NO
• 分子量: 347.312
• InChiKey: BMZIWEVJGDCPRB-MKICQXMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 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：
  6

反应信息

• 作为反应物：
  描述：

  (3E,5E)-3,5-bis(2,6-difluorobenzylidene)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(2,6-difluorobenzylidene)-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-哌啶酮 、 2,6-二氟苯甲醛 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以33%的产率得到(3E,5E)-3,5-bis(2,6-difluorobenzylidene)piperidin-4-one
  参考文献：
  名称：

  Synthesis and anti-tumor activity of EF24 analogues as IKKβ inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2017.11.077

文献信息

• Design, synthesis, and antiproliferative activity assessment of non-ATP-competitive fibroblast growth factor receptor 1 inhibitors
  作者：S. Ying、Jia Wang、C. Xu、Y. Kang、X. Zhang、L. Shi、L. Fan、Z. Wang、J. Zhou、X. Wu、J. Wu、W. Li、G. Liang

  DOI：10.1134/s1070363216120355

  日期：2016.12

  Fibroblast growth factor receptor 1 (FGFR1) is considered a therapeutic target for multiple cancers, including gastric cancer. FGFR1 inhibitors, being ATP competitors, can prevent the kinase domain and the downstream signaling cascade from phosphorylation and thus have the potential to treat cancers associated with aberrant FGFR1 activation. However, untargeted inhibition may cause numerous side effects

  成纤维细胞生长因子受体1（FGFR1）被认为是多种癌症（包括胃癌）的治疗靶标。作为ATP竞争者的FGFR1抑制剂可以防止激酶结构域和下游信号传导级联的磷酸化，因此具有治疗与异常FGFR1激活相关的癌症的潜力。但是，无针对性的抑制可能会导致许多副作用。因此，应紧急鉴定和探索非ATP竞争性FGFR1抑制剂。在这项研究中，我们设计并合成了17种去甲二氢愈创木酸（NDGA）衍生物，这是一种已知的非ATP依赖性FGFR3抑制剂。在激酶活性测定中，3,5-双（2-氟亚苄基）哌啶-4-酮（1B）在所有衍生物中显示出最高的激酶抑制活性，因此被鉴定为非ATP竞争性FGFR1抑制剂。在生物学效应评估中，1B以剂量依赖的方式抑制了FGFR-FRS2-ERK信号通路，并抑制了两种胃癌细胞的生长。总的来说，1B可被视为治疗胃癌的潜在候选药物，并且是发现新型非ATP竞争性FGFR1抑制剂的杰出先导化合物。
• 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。