(E)-3-(4-(methylamino)phenyl)-1-(4-iodophenyl)-2-propen-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(4-(methylamino)phenyl)-1-(4-iodophenyl)-2-propen-1-one
• 英文别名: (E)-1-(4-iodophenyl)-3-[4-(methylamino)phenyl]prop-2-en-1-one
• 化学式: C₁₆H₁₄INO
• 分子量: 363.198
• InChiKey: HDESUHCGHCYLHU-NYYWCZLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-(methylamino)phenyl)-1-(4-iodophenyl)-2-propen-1-one 、 联硼酸频那醇酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 以41.6%的产率得到(E)-3-(4-(methylamino)phenyl)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-propen-1-one
  参考文献：
  名称：

  Conversion of iodine to fluorine-18 based on iodinated chalcone and evaluation for β-amyloid PET imaging

  摘要：

  In the amyloid cascade hypothesis, beta-amyloid (A beta) plaques is one of the major pathological biomarkers in the Alzheimer's disease (AD) brain. We report the synthesis and evaluation of novel radiofluorinated chalcones, [F-18] 4-dimethylamino-4'-fluoro-chalcone ([F-18] DMFC) and [F-18] 4'-fluoro-4-methylamino-chalcone ([F-18] FMC), as A beta imaging probes. The conversion of iodine directly introduced to the chalcone backbone into fluorine was successfully carried out by F-18-labeling via the corresponding boronate precursors, achieving the direct introduction of fluorine-18 into the chalcone backbone to prepare [F-18] DMFC and [F-18] FMC. In a biodistribution study using normal mice, [F-18] DMFC and [F-18] FMC showed a higher initial uptake (4.43 and 5.47% ID/g at 2 min postinjection, respectively) into and more rapid clearance (0.52 and 0.66% ID/g at 30 min postinjection, respectively) from the brain than a Food and Drug Administration (FDA)-approved A beta imaging agent ([F-18] Florbetapir), meaning the improvement of the probability of detecting A beta plaques and the reduction of non-specific binding in the brain. In the in vitro binding studies using aggregates of recombinant A beta peptides, [F-18] DMFC and [F-18] FMC showed high binding affinity to recombinant A beta aggregates at the K-d values of 4.47 and 6.50 nM, respectively. In the in vitro autoradiography (ARG) experiment with AD brain sections, [F-18] DMFC and [F-18] FMC markedly accumulated only in a region with abundant A beta plaques, indicating that they clearly recognized human A beta plaques in vitro. These encouraging results suggest that [F-18] DMFC and [F-18] FMC may be promising PET probes for the detection of an amyloid pathology and the early diagnosis of AD with marked accuracy. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.05.001
• 作为产物：
  描述：

  (E)-1-(4-(tributylstannyl)phenyl)-3-(4-(methylamino)phenyl)prop-2-en-1-one 在 碘 作用下， 以 氯仿 为溶剂， 反应 0.5h， 以80.6%的产率得到(E)-3-(4-(methylamino)phenyl)-1-(4-iodophenyl)-2-propen-1-one
  参考文献：
  名称：

  Novel chalcones as probes for in vivo imaging of β-amyloid plaques in Alzheimer’s brains

  摘要：

  A novel series of chalcone derivatives for in vivo imaging beta-amyloid plaques in the brain of Alzheimer's disease (AD) were synthesized and characterized. When in vitro binding studies using A beta aggregates were carried out with chalcone derivatives, the binding affinities for A aggregate varied from 3 to 105 nM. The radioiodinated chalcones were successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives using hydrogen peroxide as the oxidant in high yields and with high radiochemical purities. Biodistribution studies in normal mice after iv injection of the radioiodinated chalcones displayed high brain uptake (2.0-4.7%ID/g at 2 min) and rapid clearance from the brain (0.2-0.6%ID/g at 30 min), which is highly desirable or amyloid imaging agents. The results in this study suggest that the novel radioiodinated chalcones may be useful amyloid imaging agents for detecting P-amyloid plaques in the brain of AD. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.052

文献信息

• Conversion of iodine to fluorine-18 based on iodinated chalcone and evaluation for β-amyloid PET imaging
  作者：Sho Kaide、Masahiro Ono、Hiroyuki Watanabe、Yoichi Shimizu、Yuji Nakamoto、Kaori Togashi、Aiko Yamaguchi、Hirofumi Hanaoka、Hideo Saji

  DOI：10.1016/j.bmc.2018.05.001

  日期：2018.7

  In the amyloid cascade hypothesis, beta-amyloid (A beta) plaques is one of the major pathological biomarkers in the Alzheimer's disease (AD) brain. We report the synthesis and evaluation of novel radiofluorinated chalcones, [F-18] 4-dimethylamino-4'-fluoro-chalcone ([F-18] DMFC) and [F-18] 4'-fluoro-4-methylamino-chalcone ([F-18] FMC), as A beta imaging probes. The conversion of iodine directly introduced to the chalcone backbone into fluorine was successfully carried out by F-18-labeling via the corresponding boronate precursors, achieving the direct introduction of fluorine-18 into the chalcone backbone to prepare [F-18] DMFC and [F-18] FMC. In a biodistribution study using normal mice, [F-18] DMFC and [F-18] FMC showed a higher initial uptake (4.43 and 5.47% ID/g at 2 min postinjection, respectively) into and more rapid clearance (0.52 and 0.66% ID/g at 30 min postinjection, respectively) from the brain than a Food and Drug Administration (FDA)-approved A beta imaging agent ([F-18] Florbetapir), meaning the improvement of the probability of detecting A beta plaques and the reduction of non-specific binding in the brain. In the in vitro binding studies using aggregates of recombinant A beta peptides, [F-18] DMFC and [F-18] FMC showed high binding affinity to recombinant A beta aggregates at the K-d values of 4.47 and 6.50 nM, respectively. In the in vitro autoradiography (ARG) experiment with AD brain sections, [F-18] DMFC and [F-18] FMC markedly accumulated only in a region with abundant A beta plaques, indicating that they clearly recognized human A beta plaques in vitro. These encouraging results suggest that [F-18] DMFC and [F-18] FMC may be promising PET probes for the detection of an amyloid pathology and the early diagnosis of AD with marked accuracy. (C) 2018 Elsevier Ltd. All rights reserved.
• Novel chalcones as probes for in vivo imaging of β-amyloid plaques in Alzheimer’s brains
  作者：Masahiro Ono、Mamoru Haratake、Hiroshi Mori、Morio Nakayama

  DOI：10.1016/j.bmc.2007.07.052

  日期：2007.11

  A novel series of chalcone derivatives for in vivo imaging beta-amyloid plaques in the brain of Alzheimer's disease (AD) were synthesized and characterized. When in vitro binding studies using A beta aggregates were carried out with chalcone derivatives, the binding affinities for A aggregate varied from 3 to 105 nM. The radioiodinated chalcones were successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives using hydrogen peroxide as the oxidant in high yields and with high radiochemical purities. Biodistribution studies in normal mice after iv injection of the radioiodinated chalcones displayed high brain uptake (2.0-4.7%ID/g at 2 min) and rapid clearance from the brain (0.2-0.6%ID/g at 30 min), which is highly desirable or amyloid imaging agents. The results in this study suggest that the novel radioiodinated chalcones may be useful amyloid imaging agents for detecting P-amyloid plaques in the brain of AD. (C) 2007 Elsevier Ltd. All rights reserved.