1-ethyl-3,5-bis(3,4,5-trimethoxybenzylidene)piperidin-4-one | 343307-76-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-ethyl-3,5-bis(3,4,5-trimethoxybenzylidene)piperidin-4-one
• 英文别名: 1-Ethyl-3,5-bis[(3,4,5-trimethoxyphenyl)methylidene]piperidin-4-one
• CAS: 343307-76-6
• 化学式: C₂₇H₃₃NO₇
• mdl: MFCD08560158
• 分子量: 483.562
• InChiKey: IOFNKUXFKVPLPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  75.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-氨基-4-甲基噻唑 、 1-ethyl-3,5-bis(3,4,5-trimethoxybenzylidene)piperidin-4-one 在 溶剂黄146 作用下， 反应 20.0h， 以40%的产率得到C₃₁H₃₇N₃O₆S
  参考文献：
  名称：

  Substituted thiazoles V. Synthesis and antitumor activity of novel thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues

  摘要：

  A novel series of thiazolo[2,3-b]quinazoline (14-23, 26 and 27), and pyrido[4,3-d]thiazolo[3,2-a] pyrimidine (34-43, 45 and 46) analogues were designed and synthesized. The obtained compounds were evaluated for their in-vitro antitumor activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Compounds 22, 38, 40 and 41 showed remarkable broad-spectrum antitumor activity. Compounds 22 and 38 are almost nine fold more active than 5-FU, with GI(50), TGI, and LC50 values of 2.5, >100, >100; and 2.4, 9.1, 36.2 mu M, respectively; while 40 and 41 are almost seven fold more active than 5-FU, with GI(50), TGI, and LC50 values of 2.9, 12.4, 46.6 and 3.0, 16.3, 54.0 mu M, respectively. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.023
• 作为产物：
  描述：

  N-乙基-4-哌啶酮 、 3,4,5-三甲氧基苯甲醛 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 1-ethyl-3,5-bis(3,4,5-trimethoxybenzylidene)piperidin-4-one
  参考文献：
  名称：

  卤化双（甲氧基亚苄基）-4-哌啶酮姜黄素具有增强的抗癌活性

  摘要：

  制备了一系列容易获得的具有卤化双（4-甲氧基/ 4,5-二甲氧基亚苄基）-4-哌啶酮结构的姜黄素，并分析了它们对五个不同实体的八种人类癌细胞系的细胞毒性影响。已知的3,4,5- trimethoxybenzylidene姜黄素2和新的双- （3-溴苯基）和二- （3,5-二溴苯基）衍生物3c中和3 d证明比针对已知类姜黄素EF24更强烈的抗增殖这些细胞系中有六个。化合物2和3c中引起活性氧物质，其在518A2黑素瘤细胞最终引起细胞凋亡的明显增加。化合物2 a阻滞G 1中的518A2黑色素瘤细胞细胞周期阶段，对转移前基质金属蛋白酶MMP-2和MMP-9的表达没有影响，而3 c导致518A2细胞在G 2 / M期积聚并下调MMP- 2表达。另外，用2a和3c处理导致HCT116细胞中集落形成的显着抑制。既2和图3c显示抗血管生成活性，例如，通过抑制在斑马鱼胚胎子肠静脉（SIV）的形成。化合物3

  DOI：

  10.1002/cmdc.201800135

文献信息

• Curcumin Analog L48H37 Prevents Lipopolysaccharide-Induced TLR4 Signaling Pathway Activation and Sepsis via Targeting MD2
  作者：Yi Wang、Xiaoou Shan、Yuanrong Dai、Lili Jiang、Gaozhi Chen、Yali Zhang、Zhe Wang、Lili Dong、Jianzhang Wu、Guilong Guo、Guang Liang

  DOI：10.1124/jpet.115.222570

  日期：2015.6

  Endotoxin-induced acute inflammatory diseases such as sepsis, mediated by excessive production of various proinflammatory cytokines, remain the leading cause of mortality in critically ill patients. Lipopolysaccharide (LPS), the characteristic endotoxin found in the outer membrane of Gram-negative bacteria, can induce the innate immunity system and through the myeloid differentiation protein 2 (MD2) and Toll-like receptor 4 (TLR4) complex, increase the production of inflammatory mediators. Our previous studies have found that a curcumin analog, L48H37 [1-ethyl-3,5-bis(3,4,5-trimethoxybenzylidene)piperidin-4-one], was able to inhibit LPS-induced inflammation, particularly tumor necrosis factor α and interleukin 6 production and gene expression in mouse macrophages. In this study, a series of biochemical experiments demonstrate L48H37 specifically targets MD2 and inhibits the interaction and signaling transduction of LPS-TLR4/MD2. L48H37 binds to the hydrophobic region of MD2 pocket and forms hydrogen bond interactions with Arg90 and Tyr102. Subsequently, L48H37 was shown to suppress LPS-induced mitogen-activated protein kinase phosphorylation and nuclear factor κ B activation in macrophages; it also dose dependently inhibits the cytokine expression in macrophages and human peripheral blood mononuclear cells stimulated by LPS. In LPS-induced septic mice, both pretreatment and treatment with L48H37 significantly improved survival and protected lung injury. Taken together, this work identified a new MD2 specific inhibitor, L48H37, as a potential candidate in the treatment of sepsis.

  内毒素诱发的急性炎症性疾病（如败血症）由各种促炎细胞因子的过度分泌所介导，仍然是危重病人死亡的主要原因。脂多糖（LPS）是革兰氏阴性细菌外膜中特有的内毒素，可诱导先天性免疫系统，并通过髓系分化蛋白 2（MD2）和 Toll 样受体 4（TLR4）复合物增加炎症介质的产生。我们之前的研究发现，姜黄素类似物 L48H37 [1-ethyl-3,5-bis(3,4,5-trimethoxybenzylidene)piperidin-4-one] 能够抑制 LPS 诱导的炎症，尤其是小鼠巨噬细胞中肿瘤坏死因子 α 和白细胞介素 6 的产生和基因表达。在本研究中，一系列生化实验证明 L48H37 能特异性地靶向 MD2，抑制 LPS-TLR4/MD2 的相互作用和信号转导。L48H37 与 MD2 口袋的疏水区域结合，并与 Arg90 和 Tyr102 形成氢键相互作用。随后的研究表明，L48H37 可抑制 LPS 诱导的巨噬细胞中丝裂原活化蛋白激酶磷酸化和核因子 κ B 的活化；它还能依赖剂量抑制受 LPS 刺激的巨噬细胞和人类外周血单核细胞中细胞因子的表达。在 LPS 诱导的败血症小鼠中，L48H37 的预处理和治疗都能显著提高存活率，保护肺损伤。综上所述，这项研究发现了一种新的 MD2 特异性抑制剂 L48H37，它是治疗败血症的潜在候选药物。
• Substituted thiazoles V. Synthesis and antitumor activity of novel thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues
  作者：Fatmah A.M. Al-Omary、Ghada S. Hassan、Shahenda M. El-Messery、Hussein I. El-Subbagh

  DOI：10.1016/j.ejmech.2011.10.023

  日期：2012.1

  A novel series of thiazolo[2,3-b]quinazoline (14-23, 26 and 27), and pyrido[4,3-d]thiazolo[3,2-a] pyrimidine (34-43, 45 and 46) analogues were designed and synthesized. The obtained compounds were evaluated for their in-vitro antitumor activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Compounds 22, 38, 40 and 41 showed remarkable broad-spectrum antitumor activity. Compounds 22 and 38 are almost nine fold more active than 5-FU, with GI(50), TGI, and LC50 values of 2.5, >100, >100; and 2.4, 9.1, 36.2 mu M, respectively; while 40 and 41 are almost seven fold more active than 5-FU, with GI(50), TGI, and LC50 values of 2.9, 12.4, 46.6 and 3.0, 16.3, 54.0 mu M, respectively. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Halogenated Bis(methoxybenzylidene)-4-piperidone Curcuminoids with Improved Anticancer Activity
  作者：Florian Schmitt、Dharmalingam Subramaniam、Shrikant Anant、Subhash Padhye、Gerrit Begemann、Rainer Schobert、Bernhard Biersack

  DOI：10.1002/cmdc.201800135

  日期：2018.6.6

  than the known curcuminoid EF24 against six of these cell lines. Compounds 2 a and 3 c caused a distinct increase of reactive oxygen species, which eventually elicited apoptosis in 518A2 melanoma cells. Compound 2 a arrested 518A2 melanoma cells in G1 phase of the cell cycle and had no effect on the expression of pro‐metastatic matrix metalloproteinases MMP‐2 and MMP‐9, whereas 3 c led to an accumulation

  制备了一系列容易获得的具有卤化双（4-甲氧基/ 4,5-二甲氧基亚苄基）-4-哌啶酮结构的姜黄素，并分析了它们对五个不同实体的八种人类癌细胞系的细胞毒性影响。已知的3,4,5- trimethoxybenzylidene姜黄素2和新的双- （3-溴苯基）和二- （3,5-二溴苯基）衍生物3c中和3 d证明比针对已知类姜黄素EF24更强烈的抗增殖这些细胞系中有六个。化合物2和3c中引起活性氧物质，其在518A2黑素瘤细胞最终引起细胞凋亡的明显增加。化合物2 a阻滞G 1中的518A2黑色素瘤细胞细胞周期阶段，对转移前基质金属蛋白酶MMP-2和MMP-9的表达没有影响，而3 c导致518A2细胞在G 2 / M期积聚并下调MMP- 2表达。另外，用2a和3c处理导致HCT116细胞中集落形成的显着抑制。既2和图3c显示抗血管生成活性，例如，通过抑制在斑马鱼胚胎子肠静脉（SIV）的形成。化合物3