EF24 | 342808-40-6

• 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: EF24
• 英文别名: 3,5-bis(2-fluorobenzylidene)-4-piperidone；3,5-bis(2-fluorobenzylidene)piperidin-4-one；3,5-bis[(2-fluorophenyl)methylidene]piperidin-4-one
• CAS: 342808-40-6
• 化学式: C₁₉H₁₅F₂NO
• 分子量: 311.331
• InChiKey: NIVYQYSNRUIFIF-UHFFFAOYSA-N

物化性质

• 溶解度：
  二甲基亚砜：≥10mg/mL

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：

  EF24 在 5% Pd(II)/C(eggshell) 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 16.0h， 以95%的产率得到(3E,5E)-3,5-bis(2-fluorobenzyl)piperidin-4-one
  参考文献：
  名称：

  CLEFMA—An anti-proliferative curcuminoid from structure–activity relationship studies on 3,5-bis(benzylidene)-4-piperidones

  摘要：

  3,5-Bis(benzylidene)-4-piperidones are being advanced as synthetic analogs of curcumin for anti-cancer and anti-inflammatory properties. We performed structure-activity relationship studies, by testing several synthesized 3,5-bis(benzylidene)-4-piperidones for anti-proliferative activity in lung adenocarcinoma H441 cells. Compared to the lead compound 1, or 3,5-bis(2-fluorobenzylidene)-4-piperidone, five compounds were found to be more potent (IC50 <30 mu M), and 16 compounds possessed reduced cell-killing efficacy (IC50 >50 mu M). Based on the observations, we synthesized 4-[3,5-bis(2-chlorobenzyl-idene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (29 or CLEFMA) as a novel analog of 1. CLEFMA was evaluated for anti-proliferative activity in H441 cells, and was found to be several folds more potent than compound 1. We did not find apoptotic cell population in flow cytometry, and the absence of apoptosis was confirmed by the lack of caspase cleavage. The electron microscopy of H441cells indicated that CLEFMA and compound 1 induce autophagic cell death that was inhibited by specific autophagy inhibitor 3-methyladenine. The results suggest that the potent and novel curcuminoid, CLEFMA, offers an alternative mode of cell death in apoptosis-resistant cancers. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.055
• 作为产物：
  描述：

  3,5-bis-(2-fluorobenzylidene)-4-piperidone acetic acid 在 potassium carbonate 作用下， 生成 EF24
  参考文献：
  名称：

  可成像姜黄素 1-[2-Aminoethyl-(6-hydrazinopyridine-3-carbamidyl)-3,5-bis-(2-fluorobenzlidene)-4-piperidone (EFAH) 的抗癌活性

  摘要：

  3,5-Bis(2-fluorobenzylidine)-4-piperidone 或 EF24 是姜黄素的有效抗癌衍生物。我们使用 EF24 的胺衍生物合成了肼烟酸共轭物 EFAH，用于 Tc-99m 放射性标记和单光子发射断层扫描成像。EFAH（3.5 mg/mL）的水溶性显着高于EF24（1.2 mg/mL）；EFAH 的辛醇/水分配系数估计为 log P = 0.33。作为一种抗增殖剂，EFAH 在抑制 H441、MiaPaCa-2 和 Panc-1 细胞增殖方面与 EF24 一样有效。在携带 Panc-1 胰腺癌异种移植物的小鼠中每日腹腔注射 EFAH（5 μg）3 周后，平均肿瘤体积减少了 79%；治疗组的肿瘤重量减少了82%。对于成像和生物分布，EFAH 用 Tc-99m (98% RCY) 标记并静脉注射给大鼠。大约 23.7% 和 14.3% 的注射剂量分别在肝脏和肠道中积累，表明

  DOI：

  10.1111/j.1747-0285.2011.01271.x

文献信息

• 3,5-Bis(2-fluorobenzylidene)-4-piperidone induce reactive oxygen species-mediated apoptosis in A549 cells
  作者：Guo-Yun Liu、Cong-Cong Jia、Pu-Ren Han、Jie Yang

  DOI：10.1007/s00044-017-2056-x

  日期：2018.1

  almost 13-fold cytotoxicity relative to curcumin against A549 cells. More importantly, 1d was more stable and more massive uptake than curcumin, which may be relationship to their cytotoxicity, apoptotic acitivity and reactive oxygen species generation. The generation of reactive oxygen species is associated with falling apart in the redox buffering system, and subsequently induces lipid peroxidation

  芳环的邻位上存在取代基有助于增强生物活性，从而突出了所谓的邻位效应。在本文中，我们合成了六个带有氟基团的单羰基姜黄素类似物，这些类似物赋予某些药物多种特性。然后，通过MTT分析评估针对A549和NCI-H460细胞的细胞毒性。结果表明，相对于姜黄素对A549细胞而言，1d表面上是一种重要的先导化合物，显示出几乎13倍的细胞毒性。更重要的是1d姜黄素比姜黄素更稳定，吸收更大，这可能与其姜黄素的细胞毒性，凋亡活性和活性氧的产生有关。活性氧的产生与氧化还原缓冲系统中的崩解有关，并随后引起脂质过氧化，线粒体膜电位的崩溃并最终导致细胞凋亡。这些数据表明邻位作用和将氟引入药物分子是提高单羰基姜黄素类似物的抗癌活性的成功策略。
• 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。
• Functionalized spirooxindole-indolizine hybrids: Stereoselective green synthesis and evaluation of anti-inflammatory effect involving TNF-α and nitrite inhibition
  作者：Raju Suresh Kumar、Paulrayer Antonisamy、Abdulrahman I. Almansour、Natarajan Arumugam、Govindasami Periyasami、Mohammad Altaf、Ha-Rim Kim、Kang-Beom Kwon

  DOI：10.1016/j.ejmech.2018.04.060

  日期：2018.5

  Stereoselective synthesis of a small library of novel spiroheterocyclic hybrids including indolizine, oxindole, and substituted piperidine units has been accomplished in [bmim]Br using a [3 + 2] cycloaddition strategy in good yield and were tested for their anti-inflammatory activities. The effects of compounds (4a-o) against inflammation were studied using carrageenan-induced hind paw oedema, croton

  使用[3 + 2]环加成策略，在[bmim] Br中完成了一个新颖的螺杂环混合物（包括吲哚利嗪，羟吲哚和取代的哌啶单元）的小型文库的立体选择性合成，并获得了良好的收率，并对其抗炎活性进行了测试。使用角叉菜胶诱导的后足水肿，巴豆油诱导的耳部水肿和棉丸诱导的肉芽肿模型研究了化合物（4a-o）对炎症的影响。在杂环杂种中，化合物4d，4g和4o对急性和慢性炎症模型表现出显着的抗炎活性。这些化合物在角叉菜胶诱导的后爪水肿中也显示出对PGE2，TNF-α和亚硝酸盐水平的显着抑制作用。因此，从我们的研究中可以明显看出，这些新型螺杂环杂种4d，4g，
• ANTIPROLIFERATIVE COMPOSITIONS COMPRISING CURCUMIN ANALOGS AND METHODS OF PRODUCING AND USING SAME
  申请人：Awasthi Vibhudutta

  公开号：US20120288555A1

  公开（公告）日：2012-11-15

  Antiproliferative compositions that include CLEFMA, as well as liposomal compositions containing said antiproliferative compositions, are disclosed. Also disclosed are methods of making and using the antiproliferative compositions and liposomal compositions.

  本文披露了包含CLEFMA的抗增殖组合物，以及含有该抗增殖组合物的脂质体组合物。还披露了制备和使用抗增殖组合物和脂质体组合物的方法。
• Antiproliferative compositions comprising curcumin analogs and methods of producing and using same
  申请人：Awasthi Vibhudutta

  公开号：US09359196B2

  公开（公告）日：2016-06-07

  Antiproliferative compositions that include CLEFMA, as well as liposomal compositions containing said antiproliferative compositions, are disclosed. Also disclosed are methods of making and using the antiproliferative compositions and liposomal compositions.

  本发明揭示了包括CLEFMA的抗增殖组合物，以及含有所述抗增殖组合物的脂质体组合物。还揭示了制备和使用抗增殖组合物和脂质体组合物的方法。