| 1636871-81-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• CAS: 1636871-81-2
• 化学式: C₁₉H₁₃F₄NO
• 分子量: 347.312
• InChiKey: IHOHSGNUAIZVRL-ACFHMISVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 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：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  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(2,5-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：

  2,5-二氟苯甲醛 、 4-氧代哌啶酮盐酸盐 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成
  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

文献信息

• 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。
• 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。