2,6-bis((E)-2,4-dimethoxybenzylidene)cyclohexanone | 462105-05-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 2,6-bis((E)-2,4-dimethoxybenzylidene)cyclohexanone
• 英文别名: (2E,6E)-2,6-bis(2,4-dimethoxybenzylidene)cyclohexanone；(2E,6E)-2,6-bis[(2,4-dimethoxyphenyl)methylidene]cyclohexan-1-one
• CAS: 462105-05-1
• 化学式: C₂₄H₂₆O₅
• 分子量: 394.467
• InChiKey: YEGAUAHKRMGQDR-KLCVKJMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-diazo-3,3-dimethylpentane-2,4-dione 、 2,6-bis((E)-2,4-dimethoxybenzylidene)cyclohexanone 在 dirhodium tetraacetate 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到
  参考文献：
  名称：

  Anomalous behaviour of Rh(II)-generated carbonyl ylides: entry into functionalized spiro dioxa-bridged polycyclic frameworks

  摘要：

  A series of symmetrical alpha,beta-unsaturated ketone systems having multiple pi-bonds were synthesized. To generate five-membered-ring carbonyl ylides as intermediates. the rhodium(II)-catalyzed reactions of alpha-diazo ketones were carried out and the carbonyl ylides reacted with the pi-bonded alpha,beta-unsaturated ketone systems. Functionalized spiro dioxa-bridged polycyclic ring systems were produced with high regio- and chemoselectivity in good yields. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)00626-3
• 作为产物：
  描述：

  环己酮 、 2,4-二甲氧基苯甲醛 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以36.2%的产率得到2,6-bis((E)-2,4-dimethoxybenzylidene)cyclohexanone
  参考文献：
  名称：

  姜黄素的单羰基类似物的合成及其对脂多糖刺激的RAW 264.7巨噬细胞释放细胞因子的抑制作用

  摘要：

  据报道姜黄素具有多功能的生物活性，特别是抑制促炎性诱导的能力。我们以前证明姜黄素的单羰基类似物在体外和体内均具有改善的药代动力学特征。在这项研究中，我们合成并检查了一系列含有5个碳连接基的姜黄素单羰基类似物，它们对LPS刺激的RAW 264.7巨噬细胞中的TNF-α和IL-6释放具有有效的抑制活性。给出了关于构效关系（SAR）的讨论和结论。被测化合物中两种最有效的类似物B75和C12，在巨噬细胞中表现出剂量依赖性的抗炎能力。这增加了姜黄素的单羰基类似物可能用作治疗各种炎性疾病的潜在药物的可能性。

  DOI：

  10.1016/j.bmc.2010.03.001

文献信息

• Synthesis of mono-carbonyl analogues of curcumin and their effects on inhibition of cytokine release in LPS-stimulated RAW 264.7 macrophages
  作者：Chengguang Zhao、Ju Yang、Yi Wang、Donglou Liang、Xuyi Yang、Xiaoxia Li、Jianzhang Wu、Xiaoping Wu、Shulin Yang、Xiaokun Li、Guang Liang

  DOI：10.1016/j.bmc.2010.03.001

  日期：2010.4

  proinflammatory induction. We previously demonstrated that the mono-carbonyl analogues of curcumin possessed improved pharmacokinetic profiles both in vitro and in vivo. In this study, we synthesized and examined a series of 5-carbon linker-containing mono-carbonyl analogues of curcumin with potent inhibitory activities against TNF-α and IL-6 release in LPS-stimulated RAW 264.7 macrophages. Discussion and conclusions

  据报道姜黄素具有多功能的生物活性，特别是抑制促炎性诱导的能力。我们以前证明姜黄素的单羰基类似物在体外和体内均具有改善的药代动力学特征。在这项研究中，我们合成并检查了一系列含有5个碳连接基的姜黄素单羰基类似物，它们对LPS刺激的RAW 264.7巨噬细胞中的TNF-α和IL-6释放具有有效的抑制活性。给出了关于构效关系（SAR）的讨论和结论。被测化合物中两种最有效的类似物B75和C12，在巨噬细胞中表现出剂量依赖性的抗炎能力。这增加了姜黄素的单羰基类似物可能用作治疗各种炎性疾病的潜在药物的可能性。
• Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors
  作者：Takahiro Hosoya、Asami Nakata、Fumie Yamasaki、Faridah Abas、Khozirah Shaari、Nordin Hj Lajis、Hiroshi Morita

  DOI：10.1007/s11418-011-0568-0

  日期：2012.1

  Anti-melanogenesis screening of 47 synthesized curcumin-like diarylpentanoid analogues was performed to show that some had a potent inhibitory effect on the melanogenesis in B16 melanoma cells. Their actions were considered to be mostly due to tyrosinase inhibition, tyrosinase expression inhibition, and melanin pigment degradation. The structure–activity relationships of those curcumin-like diarylpentanoid analogues which inhibited the melanogenesis and tyrosinase activity were also discussed. Of those compounds assayed, (2E,6E)-2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone showed the most potent anti-melanogenesis effect, the mechanism of which is considered to be the degradation of the melanin pigment in B16 melanoma cells, affecting neither the tyrosinase activity nor tyrosinase expression.

  对47种合成的姜黄素样二芳基戊烷类类似物进行了抗黑色素生成筛选，结果显示其中一些对B16黑色素瘤细胞的黑色素生成具有强抑制作用。这些作用主要被认为是通过抑制酪氨酸酶活性、抑制酪氨酸酶表达和降解黑色素色素实现的。还讨论了那些抑制黑色素生成和酪氨酸酶活性的姜黄素样二芳基戊烷类类似物的结构-活性关系。在测试的化合物中，（2E,6E）-2,6-双（2,5-二甲氧基苄叉）环己酮显示了最强的抗黑色素生成效果，其机制被认为是在B16黑色素瘤细胞中降解黑色素色素，既不影响酪氨酸酶活性也不影响酪氨酸酶表达。
• Brahmbhatt; Pandya; Patel, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 9, p. 1863 - 1867
  作者：Brahmbhatt、Pandya、Patel、Patel

  DOI：——

  日期：——
• Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
  作者：Lorraine M. Deck、Lucy A. Hunsaker、Thomas A. Vander Jagt、Lisa J. Whalen、Robert E. Royer、David L. Vander Jagt

  DOI：10.1016/j.ejmech.2017.11.048

  日期：2018.1

  Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability, to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues. (C) 2017 Published by Elsevier Masson SAS.
• Anomalous behaviour of Rh(II)-generated carbonyl ylides: entry into functionalized spiro dioxa-bridged polycyclic frameworks
  作者：Sengodagounder Muthusamy、Srinivasarao Arulananda Babu、Chidambaram Gunanathan

  DOI：10.1016/s0040-4039(02)00626-3

  日期：2002.5

  A series of symmetrical alpha,beta-unsaturated ketone systems having multiple pi-bonds were synthesized. To generate five-membered-ring carbonyl ylides as intermediates. the rhodium(II)-catalyzed reactions of alpha-diazo ketones were carried out and the carbonyl ylides reacted with the pi-bonded alpha,beta-unsaturated ketone systems. Functionalized spiro dioxa-bridged polycyclic ring systems were produced with high regio- and chemoselectivity in good yields. (C) 2002 Elsevier Science Ltd. All rights reserved.