(Z)-2,3-bis(4-benzyloxyphenyl)acrylonitrile | 868602-23-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (Z)-2,3-bis(4-benzyloxyphenyl)acrylonitrile
• 英文别名: (Z)-2,3-bis(4-phenylmethoxyphenyl)prop-2-enenitrile
• CAS: 868602-23-7
• 化学式: C₂₉H₂₃NO₂
• 分子量: 417.507
• InChiKey: HUCVCQWFEQRLKX-ZXVVBBHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Z)-2,3-bis(4-benzyloxyphenyl)acrylonitrile 在 palladium on activated charcoal copper(l) iodide 、 硼烷四氢呋喃络合物 、 二乙胺基三氟化硫 、 氢气 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.5h， 生成 (2RS,3SR)-5-fluoro-2,3-bis(4-hydroxyphenyl)pentanenitrile
  参考文献：
  名称：

  Synthesis of an Estrogen Receptor β-Selective Radioligand:  5-[¹⁸F]Fluoro-(2R*,3S*)-2,3-bis(4-hydroxyphenyl)pentanenitrile and Comparison of in Vivo Distribution with 16α-[¹⁸F]Fluoro-17β-estradiol

  摘要：

  Estrogen receptor beta (E beta), a less active ER subtype that appears to have a restraining effect on the more active ER alpha, could be a factor that determines the level of estrogen action in certain estrogen target tissues. E beta is found in breast cancer, and its levels relative to ER alpha decline with disease progression. Thus, the independent quantification of ER alpha and ER beta levels in breast cancer by imaging might be predictive of responses to different hormone therapies. To develop an imaging agent for ER beta, we synthesized a fluoroethyl. analogue of DPN (2,3-bis(4-hydroxyphenyl)propanonitrile), a known ER beta-selective ligand. This analogue, FEDPN (5-fluoro(2R*,3S*)-2,3-bis(4-hydroxyphenyl)pentanenitrile), has an 8.3-fold absolute affinity preference for ER beta. [F-18]Fluoride-labeled FEDPN was prepared from a toluenesulfonate precursor, which provided [F-18]FEDPN with a specific activity greater than 3100 Ci/mmol after HPLC purification. Biodistribution studies in immature female rats using estradiol as a blocking agent revealed specific uptake of [F-18]FEDPN in the uterus and ovaries. Experiments using ER alpha- and ER beta-knockout mice demonstrated the expected ER alpha-subtype dependence in the tissue uptake of the known 16 alpha-[F-18]fluoro-17 beta-estradiol [F-18]FES), which has a 6.3-fold preference for ER alpha. The tissue uptake of [F-18]FEDPN in the ER knockout mice showed some evidence of mediation by ERP, but the levels of specific uptake of this agent were relatively modest. Based on our results, imaging of ER alpha can be done effectively with [18F]FES, but imaging of ER beta will likely require agents with more optimized ER beta binding affinity and selectivity than [F-18]FEDNP.

  DOI：

  10.1021/jm050121f
• 作为产物：
  描述：

  4-苄氧基苯甲醛 、 4-苄氧基苯基乙腈 在 sodium methylate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以97%的产率得到(Z)-2,3-bis(4-benzyloxyphenyl)acrylonitrile
  参考文献：
  名称：

  Synthesis of an Estrogen Receptor β-Selective Radioligand:  5-[¹⁸F]Fluoro-(2R*,3S*)-2,3-bis(4-hydroxyphenyl)pentanenitrile and Comparison of in Vivo Distribution with 16α-[¹⁸F]Fluoro-17β-estradiol

  摘要：

  Estrogen receptor beta (E beta), a less active ER subtype that appears to have a restraining effect on the more active ER alpha, could be a factor that determines the level of estrogen action in certain estrogen target tissues. E beta is found in breast cancer, and its levels relative to ER alpha decline with disease progression. Thus, the independent quantification of ER alpha and ER beta levels in breast cancer by imaging might be predictive of responses to different hormone therapies. To develop an imaging agent for ER beta, we synthesized a fluoroethyl. analogue of DPN (2,3-bis(4-hydroxyphenyl)propanonitrile), a known ER beta-selective ligand. This analogue, FEDPN (5-fluoro(2R*,3S*)-2,3-bis(4-hydroxyphenyl)pentanenitrile), has an 8.3-fold absolute affinity preference for ER beta. [F-18]Fluoride-labeled FEDPN was prepared from a toluenesulfonate precursor, which provided [F-18]FEDPN with a specific activity greater than 3100 Ci/mmol after HPLC purification. Biodistribution studies in immature female rats using estradiol as a blocking agent revealed specific uptake of [F-18]FEDPN in the uterus and ovaries. Experiments using ER alpha- and ER beta-knockout mice demonstrated the expected ER alpha-subtype dependence in the tissue uptake of the known 16 alpha-[F-18]fluoro-17 beta-estradiol [F-18]FES), which has a 6.3-fold preference for ER alpha. The tissue uptake of [F-18]FEDPN in the ER knockout mice showed some evidence of mediation by ERP, but the levels of specific uptake of this agent were relatively modest. Based on our results, imaging of ER alpha can be done effectively with [18F]FES, but imaging of ER beta will likely require agents with more optimized ER beta binding affinity and selectivity than [F-18]FEDNP.

  DOI：

  10.1021/jm050121f

文献信息

• Synthesis of an Estrogen Receptor β-Selective Radioligand:  5-[¹⁸F]Fluoro-(2<i>R*</i>,3<i>S*</i>)-2,3-bis(4-hydroxyphenyl)pentanenitrile and Comparison of in Vivo Distribution with 16α-[¹⁸F]Fluoro-17β-estradiol
  作者：Jeongsoo Yoo、Carmen S. Dence、Terry L. Sharp、John A. Katzenellenbogen、Michael J. Welch

  DOI：10.1021/jm050121f

  日期：2005.10.1

  Estrogen receptor beta (E beta), a less active ER subtype that appears to have a restraining effect on the more active ER alpha, could be a factor that determines the level of estrogen action in certain estrogen target tissues. E beta is found in breast cancer, and its levels relative to ER alpha decline with disease progression. Thus, the independent quantification of ER alpha and ER beta levels in breast cancer by imaging might be predictive of responses to different hormone therapies. To develop an imaging agent for ER beta, we synthesized a fluoroethyl. analogue of DPN (2,3-bis(4-hydroxyphenyl)propanonitrile), a known ER beta-selective ligand. This analogue, FEDPN (5-fluoro(2R*,3S*)-2,3-bis(4-hydroxyphenyl)pentanenitrile), has an 8.3-fold absolute affinity preference for ER beta. [F-18]Fluoride-labeled FEDPN was prepared from a toluenesulfonate precursor, which provided [F-18]FEDPN with a specific activity greater than 3100 Ci/mmol after HPLC purification. Biodistribution studies in immature female rats using estradiol as a blocking agent revealed specific uptake of [F-18]FEDPN in the uterus and ovaries. Experiments using ER alpha- and ER beta-knockout mice demonstrated the expected ER alpha-subtype dependence in the tissue uptake of the known 16 alpha-[F-18]fluoro-17 beta-estradiol [F-18]FES), which has a 6.3-fold preference for ER alpha. The tissue uptake of [F-18]FEDPN in the ER knockout mice showed some evidence of mediation by ERP, but the levels of specific uptake of this agent were relatively modest. Based on our results, imaging of ER alpha can be done effectively with [18F]FES, but imaging of ER beta will likely require agents with more optimized ER beta binding affinity and selectivity than [F-18]FEDNP.