4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine
• 英文别名: 1-(4-Iodobenzyl)-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)piperidine；4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-[(4-iodophenyl)methyl]piperidine
• 化学式: C₂₇H₂₈F₂INO
• 分子量: 547.427
• InChiKey: NDGDCGDWGLUYKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  草酸 、 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine 以 乙醇 为溶剂， 生成 4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-(4-iodobenzyl)piperidine oxalate
  参考文献：
  名称：

  Synthesis, radiosynthesis andin vivoevaluation of [¹²³I]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine as a selective tracer for imaging the dopamine transporter

  摘要：

  多巴胺转运体（DAT）神经成像是帕金森病诊断、分期和随访的有用工具，可提供体内多巴胺能神经递质系统完整性的信息。4-(2-(双(4-氟苯基)甲氧基)乙基)-1-(4-碘苄基)哌啶（7）对 DAT 具有纳摩尔级的亲和力，与现有的 DAT SPECT 放射性配体相比，对其他单胺转运体具有更好的选择性。本研究的目的是合成并评估[123I]-7作为DAT体内示踪剂的作用。 三丁基锡前体的合成总产率为 25%。[123I]-7是通过亲电去烷基化合成的，收率为40±10%。放射化学纯度大于 98%，而比活度至少为 667 GBq/µmol。对小鼠进行的生物分布研究显示，注射后 30 秒（p.i.）和 3 小时（p.i.）的脑摄取量分别为 0.96±0.53%ID/g 和 0.26±0.02%ID/g。环孢素 A 的预处理提高了脑摄取量，表明[123I]-7 是由 P-glycoprotein (P-gp) 泵转运的。在大鼠中，[123I]-7 的区域脑分布与 DAT 分布不一致。这些结果表明，[123I]-7 不适合绘制体内 DAT 的分布图，但可以作为 P-gp 转运体的有用示踪剂。Copyright © 2009 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.1603
• 作为产物：
  描述：

  4-碘苄基溴 、 4-{2-[bis-(4-fluorophenyhl)methoxy]ethyl}piperidine oxalate 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Highly Selective Inhibitors of the Dopamine Transporter:  N-Benzylpiperidine Analogues of 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine

  摘要：

  A series of 4-[2-[bis(4-fluorophenyl)methoxylethyl-1-benzylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Binding results indicated that the presence of an electron-withdrawing group in the C-4-position of the N-benzyl group is beneficial for binding to the DAT. Several analogues have been identified with high affinity for the DAT, up to 500-fold selectivity over the SERT and about 170-fold selectivity over the NET in binding and uptake inhibition assays.

  DOI：

  10.1021/jm020419v

文献信息

• DETECTION AND TREATMENT OF RENAL CELL CARCINOMA WITH A SLC6A3 LIGAND LINKED TO A LABEL, CYTOTOXIC OR IMMUNOMODULATORY GROUP
  申请人：Akuru Pharma AB

  公开号：US20180200392A1

  公开（公告）日：2018-07-19

  The invention provides methods and material for diagnosis and treatment of ccRCC. Thus, the invention relates to a method for diagnosis or treatment of clear cell renal cell carcinoma (ccRCC) in an individual in an individual in need thereof, wherein the method comprises use of an SLC6A3 ligand linked to a radioactive label, a cytotoxic moiety or an immunomodulatory moiety.
• Structure−Activity Relationship Studies of Highly Selective Inhibitors of the Dopamine Transporter:  <i>N</i>-Benzylpiperidine Analogues of 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine
  作者：Elisabeth Greiner、Thomas Prisinzano、Edward M. Johnson、Christina M. Dersch、Jamila Marcus、John S. Partilla、Richard B. Rothman、Arthur E. Jacobson、Kenner C. Rice

  DOI：10.1021/jm020419v

  日期：2003.4.1

  A series of 4-[2-[bis(4-fluorophenyl)methoxylethyl-1-benzylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Binding results indicated that the presence of an electron-withdrawing group in the C-4-position of the N-benzyl group is beneficial for binding to the DAT. Several analogues have been identified with high affinity for the DAT, up to 500-fold selectivity over the SERT and about 170-fold selectivity over the NET in binding and uptake inhibition assays.
• Synthesis, radiosynthesis and<i>in vivo</i>evaluation of [¹²³I]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine as a selective tracer for imaging the dopamine transporter
  作者：S. De Bruyne、T. L. Boos、L. wyffels、J. L. Goeman、K. C. Rice、F. De Vos

  DOI：10.1002/jlcr.1603

  日期：2009.6.30

  Dopamine transporter (DAT) neuroimaging is a useful tool in Parkinson's disease diagnosis, staging and follow-up providing information on the integrity of the dopaminergic neurotransmitter system in vivo. 4-(2-(Bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine (7) has nanomolar affinity for DAT and better selectivity over the other monoamine transporters compared with the existing SPECT radioligands for DAT. The aim of this study was to synthesize and evaluate [123I]-7 as an in vivo tracer for DAT. The tributylstannyl precursor was synthesized with an overall yield of 25%. [123I]-7 was synthesized by electrophilic destannylation with a yield of 40±10%. Radiochemical purity appeared to be >98%, whereas specific activity was at least 667 GBq/µmol. Biodistribution studies in mice showed brain uptake of 0.96±0.53%ID/g at 30 s post injection (p.i.) and 0.26±0.02%ID/g at 3 h p.i. High blood activity was observed at all time points. Pretreatment with Cyclosporin A raised brain uptake indicating that [123I]-7 is transported by P-glycoprotein (P-gp) pumps. In rats, regional brain distribution of [123I]-7 was not in agreement with DAT distribution. These results indicate that [123I]-7 is not suitable for mapping DAT in vivo but could be a useful tracer for the P-gp transporter. Copyright © 2009 John Wiley & Sons, Ltd.

  多巴胺转运体（DAT）神经成像是帕金森病诊断、分期和随访的有用工具，可提供体内多巴胺能神经递质系统完整性的信息。4-(2-(双(4-氟苯基)甲氧基)乙基)-1-(4-碘苄基)哌啶（7）对 DAT 具有纳摩尔级的亲和力，与现有的 DAT SPECT 放射性配体相比，对其他单胺转运体具有更好的选择性。本研究的目的是合成并评估[123I]-7作为DAT体内示踪剂的作用。 三丁基锡前体的合成总产率为 25%。[123I]-7是通过亲电去烷基化合成的，收率为40±10%。放射化学纯度大于 98%，而比活度至少为 667 GBq/µmol。对小鼠进行的生物分布研究显示，注射后 30 秒（p.i.）和 3 小时（p.i.）的脑摄取量分别为 0.96±0.53%ID/g 和 0.26±0.02%ID/g。环孢素 A 的预处理提高了脑摄取量，表明[123I]-7 是由 P-glycoprotein (P-gp) 泵转运的。在大鼠中，[123I]-7 的区域脑分布与 DAT 分布不一致。这些结果表明，[123I]-7 不适合绘制体内 DAT 的分布图，但可以作为 P-gp 转运体的有用示踪剂。Copyright © 2009 John Wiley & Sons, Ltd. All Rights Reserved.