(1E,4Z,6E)-1-(3,4-dimethoxyphenyl)-7-(4-(3-fluoropropoxy)-3-methoxyphenyl)-5-hydroxy-hepta-1,4,6-trien-3-one | 1338227-31-8

• 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: (1E,4Z,6E)-1-(3,4-dimethoxyphenyl)-7-(4-(3-fluoropropoxy)-3-methoxyphenyl)-5-hydroxy-hepta-1,4,6-trien-3-one
• CAS: 1338227-31-8
• 化学式: C₂₅H₂₇FO₆
• 分子量: 442.484
• InChiKey: SVZYCOHZVISDPX-DGDMPYFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.19
• 重原子数：
  32.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  74.22
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  3,4-二甲氧基苯甲醛 在 boron trioxide 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 生成 (1E,4Z,6E)-1-(3,4-dimethoxyphenyl)-7-(4-(3-fluoropropoxy)-3-methoxyphenyl)-5-hydroxy-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

文献信息

• 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.