3,5-bis((E)-3,4-dimethoxybenzylidene)-4-methylene-1-propylpiperidine | 1434133-35-3

• 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: 3,5-bis((E)-3,4-dimethoxybenzylidene)-4-methylene-1-propylpiperidine
• 英文别名: (3E,5E)-3,5-bis(3,4-dimethoxybenzylidene)-1-propylpiperidin-4-one；(3E,5E)-3,5-bis[(3,4-dimethoxyphenyl)methylidene]-1-propylpiperidin-4-one
• CAS: 1434133-35-3
• 化学式: C₂₆H₃₁NO₅
• 分子量: 437.536
• InChiKey: UEVDRQYVQBOZRP-ZIOPAAQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-丙基-4-哌啶酮 、 3,4-二甲氧基苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以61.1%的产率得到3,5-bis((E)-3,4-dimethoxybenzylidene)-4-methylene-1-propylpiperidine
  参考文献：
  名称：

  Discovery and evaluation of piperid-4-one-containing mono-carbonyl analogs of curcumin as anti-inflammatory agents

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2013.03.057

文献信息

• 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.
• 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.