6-iodo-2-(4'-methylaminostyryl)chromone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-iodo-2-(4'-methylaminostyryl)chromone
• 英文别名: 6-iodo-4'-methylaminostyrylchromone；6-Iodo-2-(4-(methylamino)styryl)-4H-chromen-4-one；6-iodo-2-[(E)-2-[4-(methylamino)phenyl]ethenyl]chromen-4-one
• 化学式: C₁₈H₁₄INO₂
• 分子量: 403.219
• InChiKey: CAWFNCMPSJMIQH-XBXARRHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  反-4-硝基肉桂酰氯 在 四(三苯基膦)钯 吡啶 、 氢氧化钾 、 硫酸 、 sodium methylate 、 溶剂黄146 、 三乙胺 、 tin(ll) chloride 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 反应 13.67h， 生成 6-iodo-2-(4'-methylaminostyryl)chromone
  参考文献：
  名称：

  Synthesis and characterization of styrylchromone derivatives as β-amyloid imaging agents

  摘要：

  Several promising agents have been synthesized and evaluated for in vivo imaging probes of P-amyloid plaques in Alzheimer's disease (AD) brain. Recently, we have developed flavone derivatives, which possess the basic structure of the 2-phenylchromone, as useful candidates for amyloid imaging agents. In an attempt to further develop novel tracers, we synthesized and evaluated a series of 2-styrylchromone derivatives, which replace the 2-phenyl substituent of flavone backbone with the 2-styryl. A series of radioiodinated styrylchromone derivatives were designed and synthesized. The binding affinities for amyloid plaques were assessed by in vitro binding assay using pre-formed synthetic A beta(1-40) aggregates. The new series of styrylchromone derivatives showed high binding affinity to A beta aggregates at the K-d values of 32.0, 17.5 and 8.7 nM for [I-125]6, [I-125]9, and [I-125]12, respectively. In biodistribution studies using normal mice, [I-125]6 and [I-125]9 examined in normal mice displayed high brain uptakes with 4.9 and 2.8%ID/g at 2 min post injection. The radioactivity washed out from the brain rapidly (1.6 and 1.0%ID/g at 60 min post injection for [I-125]6 and [I-125]9, respectively). But [I-125]12 did not show marked brain uptake, and the washout rate from the brain was relatively slow throughout the time course (1.1 and 1.4%ID/g at 2 and 30 min post injection, respectively). Although additional modifications are necessary to improve the brain uptake and rapid clearance of non-specifically bound radiotracer, the styrylchromone backbone may be useful as a backbone structure to develop novel beta-amyloid imaging agents. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.044

文献信息

• Composition For Diagnosing Amyloid-Related Diseases
  申请人：Mori Hiroshi

  公开号：US20080131367A1

  公开（公告）日：2008-06-05

  A composition for diagnosing amyloid-related diseases, which comprises a flavone derivative, a chalcone derivative, a styrylchromone derivative, or a coumarin derivative, is provided. These compounds have high binding specificity to an amyloid β protein, high permeability to a blood-brain barrier, and ability to rapidly disappear from sites other than cerebral senile plaque. Accordingly, the composition of the present invention using these compounds enables the diagnosis of amyloid-related diseases with high precision.

  本发明提供了一种用于诊断淀粉样相关疾病的组合物，其中包括一种黄酮衍生物、一种查尔酮衍生物、一种苯乙烯基色酮衍生物或一种香豆素衍生物。这些化合物具有高结合特异性，能够与淀粉样β蛋白结合，具有高渗透性到血脑屏障，并能够迅速从除脑部老年斑以外的其他部位消失。因此，使用这些化合物的本发明组合物能够高精度地诊断淀粉样相关疾病。
• COMPOSITION FOR AMYLOID-ASSOCIATED DISEASE DIAGNOSIS
  申请人：Nagasaki University

  公开号：EP1815872A1

  公开（公告）日：2007-08-08

  A composition for diagnosing amyloid-related diseases, which comprises a flavone derivative, a chalcone derivative, a styrylchromone derivative, or a coumarin derivative, is provided. These compounds have high binding specificity to an amyloid β protein, high permeability to a blood-brain barrier, and ability to rapidly disappear from sites other than cerebral senile plaque. Accordingly, the composition of the present invention using these compounds enables the diagnosis of amyloid-related diseases with high precision.

  本研究提供了一种用于诊断淀粉样蛋白相关疾病的组合物，该组合物由黄酮衍生物、查尔酮衍生物、苯乙烯基色酮衍生物或香豆素衍生物组成。 这些化合物与淀粉样β蛋白的结合特异性高，对血脑屏障的渗透性高，能够从脑衰老斑块以外的部位迅速消失。 因此，使用这些化合物的本发明组合物能够高精度地诊断淀粉样蛋白相关疾病。
• EP1815872
  申请人：——

  公开号：——

  公开（公告）日：——
• US8192717B2
  申请人：——

  公开号：US8192717B2

  公开（公告）日：2012-06-05
• Synthesis and characterization of styrylchromone derivatives as β-amyloid imaging agents
  作者：Masahiro Ono、Yoshifumi Maya、Mamoru Haratake、Morio Nakayama

  DOI：10.1016/j.bmc.2006.09.044

  日期：2007.1.1

  Several promising agents have been synthesized and evaluated for in vivo imaging probes of P-amyloid plaques in Alzheimer's disease (AD) brain. Recently, we have developed flavone derivatives, which possess the basic structure of the 2-phenylchromone, as useful candidates for amyloid imaging agents. In an attempt to further develop novel tracers, we synthesized and evaluated a series of 2-styrylchromone derivatives, which replace the 2-phenyl substituent of flavone backbone with the 2-styryl. A series of radioiodinated styrylchromone derivatives were designed and synthesized. The binding affinities for amyloid plaques were assessed by in vitro binding assay using pre-formed synthetic A beta(1-40) aggregates. The new series of styrylchromone derivatives showed high binding affinity to A beta aggregates at the K-d values of 32.0, 17.5 and 8.7 nM for [I-125]6, [I-125]9, and [I-125]12, respectively. In biodistribution studies using normal mice, [I-125]6 and [I-125]9 examined in normal mice displayed high brain uptakes with 4.9 and 2.8%ID/g at 2 min post injection. The radioactivity washed out from the brain rapidly (1.6 and 1.0%ID/g at 60 min post injection for [I-125]6 and [I-125]9, respectively). But [I-125]12 did not show marked brain uptake, and the washout rate from the brain was relatively slow throughout the time course (1.1 and 1.4%ID/g at 2 and 30 min post injection, respectively). Although additional modifications are necessary to improve the brain uptake and rapid clearance of non-specifically bound radiotracer, the styrylchromone backbone may be useful as a backbone structure to develop novel beta-amyloid imaging agents. (c) 2006 Elsevier Ltd. All rights reserved.