N-(1-(4-iodobenzyl)piperidin-4-yl)-2-(1-oxoisoindolin-2-yl)acetamide

• 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: N-(1-(4-iodobenzyl)piperidin-4-yl)-2-(1-oxoisoindolin-2-yl)acetamide
• 英文别名: N-[1-[(4-iodophenyl)methyl]piperidin-4-yl]-2-(3-oxo-1H-isoindol-2-yl)acetamide
• 化学式: C₂₂H₂₄IN₃O₂
• 分子量: 489.356
• InChiKey: TUOYEILCEUUAJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  methyl (1-oxo-1,3-dihydro-2H-isoindol-2-yl)acetate 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.0h， 生成 N-(1-(4-iodobenzyl)piperidin-4-yl)-2-(1-oxoisoindolin-2-yl)acetamide
  参考文献：
  名称：

  Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents

  摘要：

  study reports the synthesis, [I-123]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [I-131]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [I-123]4 (ICF01012). The most favorable compounds ([I-123]20, [I-123]23, [I-123] 41, and [I-123]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [I-123]20 and [I-123]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [I-123]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [I-123]41 and [I-123]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [I-123]53 displays favorable in vivo pharrnacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [I-131] therapeutic evaluation.

  DOI：

  10.1021/acs.jmedchem.5b00777

文献信息

• Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents
  作者：Maxine P. Roberts、Vu Nguyen、Mark E. Ashford、Paula Berghofer、Naomi A. Wyatt、Anwen M. Krause-Heuer、Tien Q. Pham、Stephen R. Taylor、Leena Hogan、Cathy D. Jiang、Benjamin H. Fraser、Nigel A. Lengkeek、Lidia Matesic、Marie-Claude Gregoire、Delphine Denoyer、Rodney J. Hicks、Andrew Katsifis、Ivan Greguric

  DOI：10.1021/acs.jmedchem.5b00777

  日期：2015.8.13

  study reports the synthesis, [I-123]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [I-131]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [I-123]4 (ICF01012). The most favorable compounds ([I-123]20, [I-123]23, [I-123] 41, and [I-123]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [I-123]20 and [I-123]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [I-123]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [I-123]41 and [I-123]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [I-123]53 displays favorable in vivo pharrnacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [I-131] therapeutic evaluation.