(3E,5E)-3,5-bis(4-hydroxybenzylidene)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(4-hydroxybenzylidene)piperidin-4-one
• 英文别名: (3E,5E)-3,5-bis(4-hydroxybenzylidene)-4-piperidone；(3E,5E)-3,5-bis[(4-hydroxyphenyl)methylidene]piperidin-4-one
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: DFVFPJDIMAIJDP-KAVGSWPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 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：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3E,5E)-3,5-bis(4-hydroxybenzylidene)piperidin-4-one 在 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 48.0h， 生成 (3-{E},5-{E})-3,5-bis[(4-hydroxyphenyl)methylene]-1-[3-(4-hydroximino-1-piperidyl)propanoyl]piperidin-4-one
  参考文献：
  名称：

  新型1-[3-{3,5-双(亚苄基)-4-氧代-1-哌啶基}-3-氧代丙基]-4-哌啶酮肟及相关季铵盐的设计、合成及肿瘤选择性毒性

  摘要：

  制备了一系列新型 1-[3-{3,5-双(亚苄基)-4-氧代-1-哌啶基}-3-氧代丙基]-4-哌啶酮肟3a – h和相关季铵盐4a – h作为候选抗肿瘤药物。针对肿瘤性 Ca9-22、HSC-2 和 HSC-4 细胞的评估表明，系列3和系列4中的化合物几乎在所有情况下都是有效的细胞毒素，其 CC 50值为亚微摩尔。相比之下，这些化合物对 HGF、HPLF 和 HPC 非恶性细胞的杀细胞作用较小，显示出它们的肿瘤选择性毒性。定量结构-活性关系表明，一般来说，细胞毒性效力和选择性指数随着哈米特西格玛值大小的增加而增加。此外， 3a – h对许多白血病细胞和结肠癌细胞具有细胞毒性。 4b 、 c降低CEM细胞中的线粒体膜电位， 4d诱导Ca9-22细胞中瞬时G2/M积累。五种化合物，即3 c 、 d和4c – e ，被确定为具有药物样特性的先导分子。

  DOI：

  10.3390/molecules26237132
• 作为产物：
  描述：

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

  3,5-双（亚苄基）-4-哌啶酮和二氯乙酸的新型杂合分子，显示出强大的肿瘤选择性细胞毒性。

  摘要：

  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

  DOI：

  10.1016/j.bmcl.2019.126878

文献信息

• Design, synthesis and evaluation of novel curcumin analog as potential anti-lung cancer agent
  作者：Jing-Jing Yang、Xiao-Yan Chen、Dan-Dan Song、Li-Li Huang

  DOI：10.1080/10286020.2022.2095264

  日期：——

  limits its further clinical applications. In this study, 11 curcumin analogs with more stable scaffold were prepared and evaluated. The results indicated that the optimal compound Y-11 exhibited the strongest antiproliferative activities against lung cancer cells including H460 and H1650. Further studies showed that Y-11 potentially inhibited hDHODH, induced cell cycle arrest and apoptosis as well as

  摘要 姜黄素是一种来源于植物姜黄的多酚化合物，其结构不稳定性限制了其进一步的临床应用。在这项研究中，制备并评估了 11 种具有更稳定支架的姜黄素类似物。结果表明，最佳化合物Y-11对包括H460和H1650在内的肺癌细胞表现出最强的抗增殖活性。进一步的研究表明，Y-11可能抑制 hDHODH，诱导细胞周期停滞和细胞凋亡，并下调 H1650 细胞中关键信号通路蛋白的表达。总之，新设计的姜黄素类似物Y-11可能适用于肺癌治疗的进一步发展。
• Discovery and evaluation of piperid-4-one-containing mono-carbonyl analogs of curcumin as anti-inflammatory agents
  作者：Jianzhang Wu、Yali Zhang、Yuepiao Cai、Jian Wang、Bixia Weng、Qinqin Tang、Xiangjian Chen、Zheer Pan、Guang Liang、Shulin Yang

  DOI：10.1016/j.bmc.2013.03.057

  日期：2013.6

  We previously reported the design and discovery of three series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MCACs) as excellent anti-inflammatory agents. In continuation of our ongoing research, we designed and synthesized the fourth series of MCACs, whose central linker is a piperid-4-one. Their inhibitory effects against IL-6 production were evaluated in lipopolysaccharide (LPS)-stimulated macrophages. Among them, compounds F8, F29, F33, F35, and F36 exhibited the IC50 values under 5 mu M. The structure-activity relationship was discussed. Mechanistically, F35 and F36 dose-dependently prevented LPS-induced NF-kappa B and ERK activation. Finally, pretreatment with F35 and F36 significantly protected the C57B/L6 mice from LPS-induced septic death. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis, cytotoxicity, and structure–activity insight of NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidones
  作者：Matthew Gregory、Armaan Dandavati、Megan Lee、Samuel Tzou、Mia Savagian、Kimberly A. Brien、Vijay Satam、Pravin Patil、Moses Lee

  DOI：10.1007/s00044-013-0557-9

  日期：2013.11

  Twenty-one NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidone analogs of curcumin, 12 of which are novel, were synthesized and evaluated for their cytotoxicity against B16 (murine melanoma) and L1210 (murine lymphoma) cells grown in culture. These curcumin analogs are related to a known anticancer STAT3 inhibitor 3,5-bis-(4-fluorobenzyl)-4-piperidone (3). The compounds showed remarkable cytotoxicity, especially against B16 cells. The dimethoxy substituted analogs 4e and 4f and dihydroxy analog 4i emerged as the most active compounds with IC50 values in the range of 0.2-2.3 mu M. 4e, f, and i were about 10-times more cytotoxic against both cell lines than 3. Analysis of the results demonstrates that the position of the hydroxyl group is crucial for cytotoxicity. Amino-containing analogs are generally less active than their halogenated and oxygen-containing analogs, and N-substitution in the 4-piperidone moiety adds value to the cytotoxicity of the compounds.
• 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.