4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-3-methoxybenzaldehyde | 1338227-40-9

• 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: 4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-3-methoxybenzaldehyde
• CAS: 1338227-40-9
• 化学式: C₁₄H₁₉FO₅
• 分子量: 286.3
• InChiKey: KRKCBTPBJNXMKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.89
• 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：
  53.99
• 氢给体数：
  0.0
• 氢受体数：
  5.0

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 、 4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-3-methoxybenzaldehyde 在 boron trioxide 、 硼酸三丁酯 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以20.4%的产率得到(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：

  香草醛 在 三乙胺 、 cesium fluoride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 23.0h， 生成 4-(2-(2-(2-fluoroethoxy)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