(1E,4Z)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-hexa-1,4-dien-3-one | 1043865-68-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (1E,4Z)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-hexa-1,4-dien-3-one
• 英文别名: (1E,4Z)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)hexa-1,4-diene-3-one；(1E,4Z)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)hexa-1,4-dien-3-one；5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1,4-hexadien-3-one
• CAS: 1043865-68-4
• 化学式: C₁₃H₁₄O₄
• 分子量: 234.252
• InChiKey: UZNXOLRJQYIWAH-PKWCJPJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  17.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  66.76
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1E,4Z)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-hexa-1,4-dien-3-one 在 boron trioxide 、 硼酸三丁酯 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 乙酸乙酯 、 乙腈 为溶剂， 反应 5.5h， 生成
  参考文献：
  名称：

  Curcumin and Dehydrozingerone Derivatives:  Synthesis, Radiolabeling, and Evaluation for β-Amyloid Plaque Imaging^†

  摘要：

  Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)1,4,6-heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of AD in India. In the present study, eight novel derivatives of curcumin and 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and their binding affinities for beta-amyloid (A beta) aggregates were measured. Of these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding affinity (K-i = 0.07 nM), and therefore, 8 was radiolabeled and evaluated as a potential probe for A beta plaque imaging. Partition coefficient measurement and biodistribution in normal mice demonstrated that [F-18]8 has a suitable lipophilicity and reasonable initial brain uptake. Metabolism studies also indicated that [F-18]8 is metabolically stable in the brain. These results suggest that [F-18]8 is a suitable radioligand for A beta plaque imaging.

  DOI：

  10.1021/jm0607193
• 作为产物：
  描述：

  香草醛 、 乙酰丙酮 在 boron trioxide 、 硼酸三甲酯 、 正丁胺 、 盐酸 作用下， 以 乙酸乙酯 、 水 为溶剂， 反应 4.25h， 以50%的产率得到(1E,4Z)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-hexa-1,4-dien-3-one
  参考文献：
  名称：

  （±）-Cassumunins AC和姜黄素类似物的全合成

  摘要：

  给出了（±）-cassumunins A–C（高级抗氧化剂和抗炎剂）的总合成的完整说明。开发了两种新颖的合成cassumunins的方法。cassumunins A和B的总合成过程由已知的醛以五个线性步骤完成，总产率分别为50％和43％，具有级联[3,3]-σ位移（克莱森重排）和Heck交叉偶联反应。因此，从已知的醇以三个线性步骤完成了cassumunin C的总合成，总产率为53％。合成过程中的关键特征是串联[3,3]-向移，S N 2'反应和醛醇缩合。此外，总共合成了十八种对称和不对称姜黄素类似物。

  DOI：

  10.1055/s-0039-1690794

文献信息

• Synthesis of Non‐Symmetrical Nitrogen‐Containing Curcuminoids in the Pursuit of New Anticancer Candidates
  作者：Atiruj Theppawong、Tim Van de Walle、Charlotte Grootaert、Kristof Van Hecke、Nathalie Catry、Tom Desmet、John Van Camp、Matthias D'hooghe

  DOI：10.1002/open.201800287

  日期：2019.2

  work in our group targeted the synthesis of symmetrical azaheteroaromatic curcuminoids, which showed better solubility and cytotoxicity profiles compared to curcumin. In continuation of that work, we now focused on the synthesis of non‐symmetrical nitrogen‐containing curcuminoids bearing both a phenolic and an azaheteroaromatic moiety. In that way, we aimed to combine good solubility, antioxidant potential

  众所周知，姜黄素具有显着的抗癌作用和多种其他生物活性。然而，该分子的低生物利用度和快速代谢在其医学应用方面提出了令人担忧的问题。为了解决这个问题，姜黄素支架的结构修饰可以被设想为一种提高该化学实体的溶解度和稳定性而不损害其生物活性的策略。我们小组之前的工作目标是合成对称的氮杂芳香族姜黄素，与姜黄素相比，它表现出更好的溶解度和细胞毒性。为了继续这项工作，我们现在专注于合成带有酚类和氮杂芳香族部分的非对称含氮姜黄素。通过这种方式，我们的目标是将良好的溶解度、抗氧化潜力和细胞毒性特性结合到一个分子中。选择一些衍生物将其相当不稳定的β-二酮支架进一步化学修饰为相应的吡唑部分。通过这种方式，成功合成了 13 种新的非对称氮杂芳香族姜黄素和 4 种基于吡唑的类似物，产率为 11-69%。对所有新合成的类似物的抗氧化特性、活性氧（ROS）产生、水溶性和抗癌活性进行了评估。与姜黄素相比，几种新型衍生物表现
• BIVALENT MULTIFUNCTIONAL LIGANDS TARGETING A[BETA] OLIGOMERS AS TREATMENT FOR ALZHEIMER'S DISEASE
  申请人：Zhang Shujin

  公开号：US20130156705A1

  公开（公告）日：2013-06-20

  Bivalent multifunctional Aβ oligomerization inhibitors (BMAOIs) that target multiple risk factors involved in Alzheimer's disease are provided. The BMAOIs are useful for the treatment and/or prevention of Alzheimer's disease, as well as for diagnostic imaging of Aβ plaques in brain tissue. The BMAOIs comprise i) an Aβ oligomer (ApO)-inhibitor moiety which may have antioxidant activity (e.g. curcumin, curcumin derivatives, curcumin hybrids, resveratrol, etc.); ii) a cell membrane/lipid raft (CM/LR) anchoring moiety (e.g. cholesterol, cholesterylamine, a steroid, etc.); and iii) a spacer or linker moiety that stably links i)

  提供了针对多个阿尔茨海默病风险因素的二价多功能Aβ寡聚体化抑制剂（BMAOI）。BMAOI对于阿尔茨海默病的治疗和/或预防以及Aβ斑块在脑组织中的诊断成像具有用途。BMAOI包括：i）Aβ寡聚体（ApO）抑制剂基团，可能具有抗氧化活性（例如姜黄素，姜黄素衍生物，姜黄素杂合物，白藜芦醇等）；ii）细胞膜/脂 rafts（CM / LR）锚定基团（例如胆固醇，胆固醇胺，类固醇等）；和iii）稳定连接i）和ii）的间隔或连接基团。
• Synthesis and evaluation of 1-(4-[18F]fluoroethyl)-7-(4′-methyl)curcumin with improved brain permeability for β-amyloid plaque imaging
  作者：Iljung Lee、Jehoon Yang、Jung Hee Lee、Yearn Seong Choe

  DOI：10.1016/j.bmcl.2011.08.003

  日期：2011.10

  Alzheimer's disease is characterized by the accumulation of beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in the brain. We previously developed [F-18]fluoropropylcurcumin ([F-18]FP-curcumin), which demonstrated excellent binding affinity (K-i = 0.07 nM) for A beta(1-40) aggregates and good pharmacokinetics in normal mouse brains. However, its initial brain uptake was poor (0.52% ID/g at 2 min post-injection). Therefore, in the present study, fluorine-substituted 4,4'-bissubstituted or pegylated curcumin derivatives were synthesized and evaluated. Their binding affinities for A beta(1-42) aggregates were measured and 1-(4-fluoroethyl)-7-(4'-methyl) curcumin (1) had the highest binding affinity (K-i = 2.12 nM). Fluorescence staining of Tg APP/PS-1 mouse brain sections demonstrated high and specific labeling of A beta plaques by 1 in the cortex region, which was confirmed with thioflavin-S staining of the same spots in the adjacent brain sections. Radioligand [F-18]1 was found to have an appropriate partition coefficient (logP(o/w) = 2.40), and its tissue distribution in normal mice demonstrated improved brain permeability (1.44% ID/g at 2 min post-injection) compared to that of [F-18]FP-curcumin by a factor of 2.8 and fast wash-out from mouse brains (0.45% ID/g at 30 min post-injection). These results suggest that [F-18]1 may hold promise as a PET radioligand for A beta plaque imaging. (C) 2011 Elsevier Ltd. All rights reserved.
• DRUG COMPOSITION FOR PARENTERAL ADMINISTRATION
  申请人：THERABIOPHARMA INC.

  公开号：US20190224325A1

  公开（公告）日：2019-07-25

  Provided is a curcumin pharmaceutical preparation that is highly water soluble, can maintain the concentration of free curcumin in the blood sufficiently high by being administered parenterally, can effectively obtain a pharmacological action of curcumin, and is highly safe. A pharmaceutical composition for parenteral administration, including a water-soluble substance conjugate of curcumin as an active component.
• US9260473B2
  申请人：——

  公开号：US9260473B2

  公开（公告）日：2016-02-16