(3E,5E)-3,5-bis(3,4-dimethoxybenzylidene)-1-ethylpiperidin-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3E,5E)-3,5-bis(3,4-dimethoxybenzylidene)-1-ethylpiperidin-4-one
• 英文别名: 3,5-bis((E)-3,4-dimethoxybenzylidene)-1-ethylpiperidin-4-one；3,5-bis(3,4-dimethoxybenzylidene)-1-ethylpiperidin-4-one；(3E,5E)-3,5-bis[(3,4-dimethoxyphenyl)methylidene]-1-ethylpiperidin-4-one
• 化学式: C₂₅H₂₉NO₅
• 分子量: 423.509
• InChiKey: SYNCWLVIOGZJCG-AYKLPDECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  丙二腈 、 (3E,5E)-3,5-bis(3,4-dimethoxybenzylidene)-1-ethylpiperidin-4-one 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以75%的产率得到2-Amino-4-(3,4-dimethoxy-phenyl)-8-[1-(3,4-dimethoxy-phenyl)-meth-(E)-ylidene]-6-ethyl-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridine-3-carbonitrile
  参考文献：
  名称：

  Hammam; Sharaf; Abd El-Hafez, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 3, p. 213 - 221

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4-二甲氧基苯甲醛 在 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 mineral oil 为溶剂， 反应 12.5h， 生成 (3E,5E)-3,5-bis(3,4-dimethoxybenzylidene)-1-ethylpiperidin-4-one
  参考文献：
  名称：

  Design, synthesis, anti-lung cancer activity, and chemosensitization of tumor-selective MCACs based on ROS-mediated JNK pathway activation and NF-κB pathway inhibition

  摘要：

  EF24 and F35 both were effective monocarbonyl curcumin analogues (MCACs) with excellent anti-tumor activity, however, drug defect such as toxicity may limit their further development. To get anti-lung cancer drugs with high efficiency, low toxicity and chemosensitization, a series of analogues based on EF24 and F35 were designed and synthesized. A number of compounds were found to exhibit cytotoxic activities selectively towards lung cancer cells compared to normal cells. Among these compounds, 5B was considered as an optimal anti-tumor agent for lung cancer cells with IC50 values ranging from 1.0 to 1.7 mu M, selectivity index (SI, as a logarithm of a ratio of IC50 value for normal and cancer cells) were all above 1.1, while the SI of EF24 and F35 were less than 0.8. Consistent with selectivity in vitro, 5B was observed to show lower toxicity in acute toxicity experiment than EF24 and F35 respectively. Further, 5B was found to exert anti-tumor effects through ROS-mediated activation of JNK pathway and inhibition of NF-kappa B pathway. 5B could significantly enhance the sensitivity of A549 cells to cisplatin or 5-Fu. These findings suggested that 5B was an effective and less toxic MCAC and provided a promising candidate for anti-tumor drugs. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.051

文献信息

• 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。
• 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.
• Hammam; Sharaf; Abd El-Hafez, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 3, p. 213 - 221
  作者：Hammam、Sharaf、Abd El-Hafez

  DOI：——

  日期：——
• Design, synthesis, anti-lung cancer activity, and chemosensitization of tumor-selective MCACs based on ROS-mediated JNK pathway activation and NF-κB pathway inhibition
  作者：Liping Chen、Qian Li、Bixia Weng、Jiabing Wang、Yangyang Zhou、Dezhi Cheng、Thanchanok Sirirak、Peihong Qiu、Jianzhang Wu

  DOI：10.1016/j.ejmech.2018.03.051

  日期：2018.5

  EF24 and F35 both were effective monocarbonyl curcumin analogues (MCACs) with excellent anti-tumor activity, however, drug defect such as toxicity may limit their further development. To get anti-lung cancer drugs with high efficiency, low toxicity and chemosensitization, a series of analogues based on EF24 and F35 were designed and synthesized. A number of compounds were found to exhibit cytotoxic activities selectively towards lung cancer cells compared to normal cells. Among these compounds, 5B was considered as an optimal anti-tumor agent for lung cancer cells with IC50 values ranging from 1.0 to 1.7 mu M, selectivity index (SI, as a logarithm of a ratio of IC50 value for normal and cancer cells) were all above 1.1, while the SI of EF24 and F35 were less than 0.8. Consistent with selectivity in vitro, 5B was observed to show lower toxicity in acute toxicity experiment than EF24 and F35 respectively. Further, 5B was found to exert anti-tumor effects through ROS-mediated activation of JNK pathway and inhibition of NF-kappa B pathway. 5B could significantly enhance the sensitivity of A549 cells to cisplatin or 5-Fu. These findings suggested that 5B was an effective and less toxic MCAC and provided a promising candidate for anti-tumor drugs. (C) 2018 Elsevier Masson SAS. All rights reserved.