(E)-3-(4-(methylamino)phenyl)-1-(4-fluorophenyl)-2-propen-1-one | 958456-79-6

• 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-fluorophenyl)-2-propen-1-one
• 英文别名: (E)-1-(4-fluorophenyl)-3-(4-methylaminophenyl)-2-propen-1-one；(E)-1-(4-fluorophenyl)-3-(4-(methylamino)phenyl)prop-2-en-1-one；(E)-1-(4-fluorophenyl)-3-[4-(methylamino)phenyl]prop-2-en-1-one
• CAS: 958456-79-6
• 化学式: C₁₆H₁₄FNO
• 分子量: 255.292
• InChiKey: UXBFZYLATLFUCW-NYYWCZLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 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：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-(methylamino)phenyl)-1-(4-fluorophenyl)-2-propen-1-one 、 [11C]methyl triflate 以 丁酮 为溶剂， 反应 0.05h， 生成 (E)-1-(4-fluorophenyl)-3-[4-[methyl((111C)methyl)amino]phenyl]prop-2-en-1-one
  参考文献：
  名称：

  COMPOSITION FOR DIAGNOSING AMYLOID-RELATED DISEASE

  摘要：

  提供了一种化合物组合物，其由一般式（I）表示的化合物组成，其中R1代表5-碘噻吩-2-基基团或类似物，R2代表4-二甲氨基苯基团或类似物。该组合物对于诊断与淀粉样蛋白相关的疾病，如阿尔茨海默病，具有高结合特异性，高透过血脑屏障的渗透性，以及在大脑老年斑以外部位迅速被排除的特性。

  公开号：

  EP2030635A1
• 作为产物：
  描述：

  4-甲基氨基苯甲醛 、 4-氟苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 9.17h， 以76.7%的产率得到(E)-3-(4-(methylamino)phenyl)-1-(4-fluorophenyl)-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

文献信息

• COMPOSITION FOR DIAGNOSIS OF AMYLOID-RELATED DISEASE
  申请人：Nakayama Morio

  公开号：US20100278733A1

  公开（公告）日：2010-11-04

  There is provided a composition comprising a compound represented by general formula (I), wherein R l represents a 5-iodothiophen-2-yl group or the like, and R 2 represents a 4-dimethylaminophenyl group or the like. This composition is useful for diagnosis of an amyloid-related disease such as Alzheimer's disease because the compound has high binding specificity to amyloid β protein, high permeability through the blood-brain barrier, and a property of being rapidly eliminated from sites other than senile plaques in the brain.

  提供了一种化合物组合物，其由一般式(I)所代表的化合物组成，其中R1代表5-碘噻吩-2-基基团或类似物，R2代表4-二甲氨基苯基基团或类似物。该组合物对于诊断与淀粉样蛋白相关的疾病，如阿尔茨海默病，具有高结合特异性，高透过血脑屏障的渗透性，以及在大脑老年斑以外的部位迅速被排除的特性。
• Fluoro-pegylated Chalcones as Positron Emission Tomography Probes for in Vivo Imaging of β-Amyloid Plaques in Alzheimer’s Disease
  作者：Masahiro Ono、Rumi Watanabe、Hidekazu Kawashima、Yan Cheng、Hiroyuki Kimura、Hiroyuki Watanabe、Mamoru Haratake、Hideo Saji、Morio Nakayama

  DOI：10.1021/jm901057p

  日期：2009.10.22

  This paper describes the synthesis and biological evaluation of fluoro-pegylated (FPEG) chalcones for the imaging of β-amyloid (Aβ) plaques in patients with Alzheimer’s disease (AD). FPEG chalcone derivatives were prepared by the aldol condensation reaction. In binding experiments conducted in vitro using Aβ(1−42) aggregates, the FPEG chalcone derivatives having a dimethylamino group showed higher

  本文描述了氟聚乙二醇化（FPEG）查耳酮对阿尔茨海默病（AD）患者的β-淀粉样蛋白（Aβ）斑块成像的合成和生物学评估。通过羟醛缩合反应制备FPEG查尔酮衍生物。在使用Aβ（1-42）聚集体的结合在体外进行的实验，具有二甲基氨基的FPEG查耳酮衍生物显示出更高的ķ我比那些具有单甲基或伯胺基团的值（20-50纳米）。当在正常小鼠中检查具有二甲氨基的11 C标记的FPEG查尔酮衍生物的生物分布时，发现所有四种衍生物都具有足够的摄取以使大脑中的Aβ斑成像。18 F标记的7c尽管观察到11 C和18 F示踪剂之间存在细微差别，但也显示出良好的被大脑吸收和清除的能力。当使用AD模型小鼠和AD患者的脑切片进行Aβ斑块的标记时，FPEG查尔酮衍生物7c强烈标记了Aβ斑块。两者合计，结果表明7c是检测AD患者大脑中Aβ斑块的有用候选PET示踪剂。
• COMPOSITION FOR DIAGNOSING AMYLOID-RELATED DISEASE
  申请人：Nagasaki University

  公开号：EP2030635A1

  公开（公告）日：2009-03-04

  There is provided a composition comprising a compound represented by general formula (I), wherein R1 represents a 5-iodothiophen-2-yl group or the like, and R2 represents a 4-dimethylaminophenyl group or the like. This composition is useful for diagnosis of an amyloid-related disease such as Alzheimer's disease because the compound has high binding specificity to amyloid β protein, high permeability through the blood-brain barrier, and a property of being rapidly eliminated from sites other than senile plaques in the brain.

  提供了一种化合物组合物，其由一般式（I）表示的化合物组成，其中R1代表5-碘噻吩-2-基基团或类似物，R2代表4-二甲氨基苯基团或类似物。该组合物对于诊断与淀粉样蛋白相关的疾病，如阿尔茨海默病，具有高结合特异性，高透过血脑屏障的渗透性，以及在大脑老年斑以外部位迅速被排除的特性。
• 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.