H-4073 | 330450-40-3

• 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: H-4073
• 英文别名: 3,5-bis(4-fluorobenzylidene)-4-oxopiperidine；3,5-bis(4-fluorobenzylidene)-4-piperidone；3,5-Bis[(4-fluorophenyl)methylidene]piperidin-4-one
• CAS: 330450-40-3
• 化学式: C₁₉H₁₅F₂NO
• 分子量: 311.331
• InChiKey: ASJBYMPCFLKDGD-UHFFFAOYSA-N

物化性质

• 熔点：
  236.8 °C
• 沸点：
  496.6±45.0 °C(Predicted)
• 密度：
  1.281±0.06 g/cm3(Predicted)

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：

  H-4073 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  姜黄素硼酸衍生物,其制备方法和应用

  摘要：

  本发明涉及通式(I)所示的化合物或其药学上可接受的盐或溶剂化物，还涉及上述化合物的制备方法及其在制备作为19S蛋白酶体抑制剂的药物方面的用途。

  公开号：

  CN106146542A
• 作为产物：
  描述：

  3,5-bis(4-fluorobenzylidene)piperidin-4-one hydrochloride 在 potassium carbonate 作用下， 以1.4 g的产率得到H-4073
  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

文献信息

• Synthesis, human topoisomerase IIα inhibitory properties and molecular modeling studies of anti-proliferative curcumin mimics
  作者：Nehmedo G. Fawzy、Siva S. Panda、Walid Fayad、ElSayed M. Shalaby、Aladdin M. Srour、Adel S. Girgis

  DOI：10.1039/c9ra05661k

  日期：——

  Piperidinecarboxamides (curcumin mimics) show promising anti-proliferative properties against HCT116 (colon), MCF7 (breast) and A431 (squamous skin) carcinoma cell lines with potency higher than that of 5-fluorouracil.

  吡啶甲酰胺（姜黄素类似物）显示出对HCT116（结肠）、MCF7（乳腺）和A431（鳞状皮肤）癌细胞系有很好的抗增殖特性，其效力高于5-氟尿嘧啶。
• A One-Pot Three-Component Synthesis and Investigation of the In Vitro Mechanistic Anticancer Activity of Highly Functionalized Spirooxindole-Pyrrolidine Heterocyclic Hybrids
  作者：Raju Suresh Kumar、Dhaifallah M. Al-thamili、Abdulrahman I. Almansour、Natarajan Arumugam、Faruq Mohammad

  DOI：10.3390/molecules25235581

  日期：——

  good yields through a one-pot three-component (3+2) cycloaddition strategy. The synthesized compounds were characterized thoroughly for the physicochemical properties by making use of FT-IR, NMR spectroscopy, and mass spectrometry. Further, these compounds have been evaluated for the influence of anticancer activity against HepG2 cells up to 200 µg/mL concentration. The highly active molecular scaffold

  为了开发具有独特作用机制的更有效且价格合理的抗癌剂，我们通过一锅三组分 (3+2) 环加成策略以良好的收率设计并合成了螺羟吲哚-吡咯烷杂环杂化物的衍生物。利用傅立叶变换红外光谱、核磁共振光谱和质谱对合成化合物的理化性质进行了彻底的表征。此外，还评估了这些化合物对浓度高达 200 µg/mL 的 HepG2 细胞的抗癌活性的影响。对高活性分子支架进行了深入的机理研究，发现细胞死亡的主要途径是细胞凋亡，细胞凋亡是通过诱导活性氧并随后参与半胱天冬酶而发生的。
• Synthesis, Biological Evaluation and Molecular Docking Studies Against EGFR Tyrosine Kinase of 3,5-bis(substituted benzylidene)-1- ethylpiperidin-4-one Analogues
  作者：Mohamed Jawed Ahsan、Deepak Saini、Piush Sharma、Surender Singh Jadav、Mohammad Afroz Bakht、Salahuddin、Ramesh Alluri、Md Faiyazuddin

  DOI：10.2174/1570178617999201020220400

  日期：2021.7.29

  The compound 4g showed significant anticancer activity with GI₅₀ of 28.2 μM against MCF-7 (Breast cancer cell line). The antioxidant activity of compound 4g (IC₅₀ = 14.98±0.91 μM) was found to be comparable to the standard drug ascorbic acid. The binding modes of compounds 4a-g against the molecular target EGFR tyrosine kinase were also studied. The structure-activity relationship (SAR) was also studied.

  The compound 4g showed significant anticancer activity with GI₅₀ of 28.2 μM against MCF-7 (Breast cancer cell line). The antioxidant activity of the compound, 4g was found to be comparable to the standard drug ascorbic acid, while its anticancer activity was found to be less than that of the standard drug adriamycin.

  癌症是死亡的主要原因之一。本研究的目的是合成和研究一些3,5-双(取代苯甲醛基)-1-乙基哌啶-4-酮类似物(4a-g)的抗癌和抗氧化活性。 3,5-双(取代苯甲醛基)-1-乙基哌啶-4-酮类似物(4a-g)是从前体哌啶-4-酮盐酸盐(1)制备而来。首先合成中间体3,5-双(取代苯甲醛基)哌啶-4-酮类似物(3a-g)，然后在丙酮和K2CO3中与C2H5I进行乙基化反应，得到目标化合物(4a-g)。傅里叶变换红外(FTIR)、核磁共振(1H和13C NMR)、质谱和显微分析被用来表征目标化合物(4a-g)。所有化合物都通过SRB测定和NCI US方案进行了抗癌活性评估，通过DPPH自由基测定进行了抗氧化活性评估。所有目标化合物(4a-g)还被用于分子对接研究，以研究我们的化合物与分子靶点的可能相互作用方式。 化合物4g对MCF-7(乳腺癌细胞系)显示出显著的抗癌活性，GI50为28.2μM。化合物4g的抗氧化活性(IC50 = 14.98±0.91μM)与标准药物抗坏血酸相当。还研究了化合物4a-g与分子靶点EGFR酪氨酸激酶的结合模式，同时还研究了结构-活性关系(SAR)。 化合物4g对MCF-7(乳腺癌细胞系)显示出显著的抗癌活性，GI50为28.2μM。化合物4g的抗氧化活性与标准药物抗坏血酸相当，而其抗癌活性则低于标准药物阿霉素。
• Tumour-specific cytotoxicity and structure–activity relationships of novel 1-[3-(2-methoxyethylthio)propionyl]-3,5-bis(benzylidene)-4-piperidones
  作者：Mohammad Hossain、Umashankar Das、Naoki Umemura、Hiroshi Sakagami、Jan Balzarini、Erik De Clercq、Masami Kawase、Jonathan R. Dimmock

  DOI：10.1016/j.bmc.2016.03.056

  日期：2016.5

  piperidones 3-7 were designed and synthesized as novel cytotoxic agents. These compounds displayed potent cytotoxic properties towards human Molt4/C8, CEM, HSC-2, HSC-3 and HSC-4 neoplasms and also to murine L1210 cells. The majority of the compounds have sub-micromolar or very low micromolar IC50 and CC50 values and are significantly more potent than the reference alkylating drug melphalan. Evaluation

  设计并合成了一系列1-酰基-3,5-双（亚苄基）-4-哌啶酮3-7，作为新型细胞毒性剂。这些化合物对人Molt4 / C8，CEM，HSC-2，HSC-3和HSC-4肿瘤以及对鼠L1210细胞均显示出强大的细胞毒性。大多数化合物具有亚微摩尔或非常低的微摩尔IC50和CC50值，并且比参考烷基化药物美法仑显着更有效。这些化合物针对非恶性HGF和HPLF细胞的评估显示了肿瘤特异性毒性。特别地，3e作为有希望的铅细胞毒剂出现，它引起HSC-2细胞凋亡和PARP1裂解。
• Design, synthesis, and biological evaluation of novel &lt;strong&gt;EF24 &lt;/strong&gt;and &lt;strong&gt;EF31 &lt;/strong&gt;analogs as potential I&amp;kappa;B kinase &amp;beta; inhibitors for the treatment of pancreatic cancer
  作者：Xuemeng Xie、Jinfu Tu、Heyi You、Bingren Hu

  DOI：10.2147/dddt.s133172

  日期：——

  Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31, exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular

  鉴于抑制性κB（IκB）激酶β（IKKβ）在胰腺癌（PC）的发展和进程中发挥着重要作用，人们认为靶向IKKβ的抑制剂作为新型抗PC疗法越来越受欢迎。就抑制IKKβ活性和PC细胞增殖而言，两种名为EF24和EF31的合成分子表现出有利的潜力。为了增强它们的细胞效力并分析它们的结构-活性关系，设计并合成了四个系列的EF24和EF31类似物。通过激酶活性和癌细胞的活力筛选，D6对IKKβ活性和PC细胞增殖均表现出出色的抑制作用。此外，多项生物学评估表明，D6直接与IKKβ结合，并显着抑制肿瘤坏死因子-α诱导的IKKβ/核因子κB通路的激活，并有效诱导癌细胞凋亡。此外，分子对接和分子动力学模拟分析表明，D6和IKKβ之间的主导力包括疏水相互作用。总之，D6可能是PC治疗的有前途的治疗剂，它也为新型IKKβ抑制剂的设计提供了结构上的线索。