4-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)-3-methoxybenzaldehyde | 1338227-36-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)-3-methoxybenzaldehyde
• CAS: 1338227-36-3
• 化学式: C₁₄H₂₀O₆
• 分子量: 284.309
• InChiKey: XBQUXNGZIGKZPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.91
• 重原子数：
  20.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74.22
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)-3-methoxybenzaldehyde 在 boron trioxide 、 三乙胺 、 cesium fluoride 作用下， 以 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 19.0h， 生成 (1E,4Z,6E)-7-(4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-3-methoxyphenyl)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one
  参考文献：
  名称：

  Synthesis and evaluation of 1-(4-[18F]fluoroethyl)-7-(4′-methyl)curcumin with improved brain permeability for β-amyloid plaque imaging

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2011.08.003
• 作为产物：
  描述：

  2-氯乙氧基-2-乙氧基二乙醇 、 香草醛 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以67%的产率得到4-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)-3-methoxybenzaldehyde
  参考文献：
  名称：

  Synthesis and evaluation of 1-(4-[18F]fluoroethyl)-7-(4′-methyl)curcumin with improved brain permeability for β-amyloid plaque imaging

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2011.08.003

文献信息

• Synthesis, Characterization, and Biological Evaluation of Meldrum’s Acid Derivatives: Dual Activity and Molecular Docking Study
  作者：Syed Nasir Abbas Bukhari、Mohamed Abdelwahab Abdelgawad、Naveed Ahmed、Muhammad Wahab Amjad、Muhammad Ajaz Hussain、Mervat A. Elsherif、Hasan Ejaz、Nasser H. Alotaibi、Ignjat Filipović、Nenad Janković

  DOI：10.3390/ph16020281

  日期：——

  Meldrum’s acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum’s acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison

  在本研究中，合成了八种含有各种香草基的新型 Meldrum 酸衍生物。 Vanillilidene Meldrum 的酸性化合物针对不同的癌细胞系和微生物进行了测试。在九个中，三个对大肠杆菌、HeLa 和 A549 细胞系表现出非常好的生物活性。结果表明，与O-酰基取代的衍生物相比，O-烷基取代的衍生物具有更好的抗菌和抗癌活性。癸基取代的分子 (3i) 对大肠杆菌 (MIC = 12.4 μM) 和癌细胞系（HeLa、A549 和 LS174 分别 = 15.7、21.8 和 30.5 μM）具有最高活性。 3i 的选择性指数为 4.8 (HeLa)。分子对接研究表明，化合物 3i 对 DNA、大肠杆菌旋转酶 B 和拓扑异构酶 II β 表现出良好的结合亲和力。共价对接表明 3i 是亲核试剂 Lys 和 Ser 的迈克尔受体。最佳 Eb 为拓扑异构酶 II beta-LYS482-3i 簇。