[¹¹C]-N-desmethyl-loperamide | 1067642-12-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [¹¹C]-N-desmethyl-loperamide
• 英文别名: Desmethylloperamide C-11；4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N-(111C)methyl-2,2-diphenylbutanamide
• CAS: 1067642-12-9
• 化学式: C₂₈H₃₁ClN₂O₂
• 分子量: 462.008
• InChiKey: ZMOPTLXEYOVARP-BJUDXGSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [¹¹C]-N-desmethyl-loperamide 、 氢氧化钾 以 叔丁醇 为溶剂， 反应 72.0h， 以gave the required precursor (4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylbutanamide的产率得到4-[4-(4-氯苯基)-4-羟基-1-哌啶基]-2,2-二苯基丁酰胺
  参考文献：
  名称：

  Radiotracers for imaging P-glycoprotein function

  摘要：

  P-糖蛋白转运体（P-gp）在血脑屏障上起泵的作用，排除各种异物（如毒素、药物等）进入大脑，并且在肿瘤中表达，以应对已知或可能的化疗药物（这种现象称为多药耐药）。本发明涉及制备和使用放射示踪剂来体外和体内成像P-gp功能。本发明的放射示踪剂是P-gp的亲和底物，并且基于N-去甲基-洛哌丁的结构。

  公开号：

  US07989630B2
• 作为产物：
  描述：

  4-[4-(4-氯苯基)-4-羟基-1-哌啶基]-2,2-二苯基丁酰胺 、 [11C]methyl iodide 在 氢氧化钾 作用下， 以 二甲基亚砜 为溶剂， 反应 0.08h， 生成 [¹¹C]-N-desmethyl-loperamide
  参考文献：
  名称：

  Synthesis and Evaluation of [N-methyl-¹¹C]N-Desmethyl-loperamide as a New and Improved PET Radiotracer for Imaging P-gp Function

  摘要：

  [C-11]Loperamide has been proposed for imaging P-glycoprotein (P-gp) function with positron emission tomography (PET), but its metabolism to [N-methyl-C-11]N-desmethyl-loperamide ([C-11]dLop; [C-11]3) precludes quantification. We considered that [C-11]3 might itself be a superior radiotracer for imaging brain P-gp function and therefore aimed to prepare [C-11]3 and characterize its efficacy. An amide precursor (2) was synthesized and methylated with [C-11]iodomethane to give [C-11]3. After administration of [C-11]3 to wild-type mice, brain radioactivity uptake was very low. In P-gp (mdr-la(-/-)) knockout mice, brain uptake of radioactivity at 30 min increased about 3.5-fold by PET measures, and over 7-fold by ex vivo measures. In knockout mice, brain radioactivity was predominantly (90%) unchanged radiotracer. In monkey PET experiments, brain radioactivity uptake was also very low but after P-gp blockade increased more than 7-fold. [C-11]3 is an effective new radiotracer for imaging brain P-gp function and, in favor of future successful quantification, appears free of extensive brain-penetrant radiometabolites.

  DOI：

  10.1021/jm800510m

文献信息

• RADIOTRACERS FOR IMAGING P-GLYCOPROTEIN FUNCTION
  申请人：Pike Victor W.

  公开号：US20090274624A1

  公开（公告）日：2009-11-05

  P-glycoprotein transporter (P-gp) acts as a pump at the blood-brain barrier to exclude a wide range of xenobiotics (e.g., toxins, drugs, etc.) from the brain and is also expressed in a tumor in response to exposure to established or prospective chemotherapeutics (a phenomenon known as multidrug resistance). This invention concerns the preparation and use of radiotracers for imaging P-gp function in vitro and in vivo. Radiotracers of the present invention are avid substrates for P-gp and have structures based on N-Desmethyl-loperamide.

  P-糖蛋白转运体（P-gp）在血脑屏障处作为泵，排除大范围的异物（例如毒素、药物等）进入大脑，并且在肿瘤中响应已建立或预期化疗药物的暴露而表达（这种现象称为多药耐药）。本发明涉及制备和使用放射示踪剂来在体外和体内成像P-gp功能。本发明的放射示踪剂是P-gp的亲和底物，并且基于N-去甲基-洛哌丁的结构。
• A high-yield route to synthesize the P-glycoprotein radioligand [ C]N-desmethyl-loperamide and its parent radioligand [ C]loperamide
  作者：Min Wang、Mingzhang Gao、Qi-Huang Zheng

  DOI：10.1016/j.bmcl.2013.08.024

  日期：2013.10

  N-Desmethyl-loperamide and loperamide were synthesized from a, a-diphenyl-c-butyrolactone and 4-(4-chlorophenyl)-4-hydroxypiperidine in five and four steps with 8% and 16% overall yield, respectively. The amide precursor was synthesized from 4-bromo-2,2-diphenylbutyronitrile and 4-(4-chlorophenyl)-4-hydroxypiperidine in 2 steps with 21-57% overall yield. [C-11] N-Desmethyl-loperamide and [C-11] loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [C-11] CH3OTf through N-[C-11] methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [C-11] CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/lmol specific activity at EOB. (C) 2013 Elsevier Ltd. All rights reserved.
• US7989630B2
  申请人：——

  公开号：US7989630B2

  公开（公告）日：2011-08-02
• Synthesis and Evaluation of [<i>N-</i>methyl-¹¹C]<i>N</i>-Desmethyl-loperamide as a New and Improved PET Radiotracer for Imaging P-gp Function
  作者：Neva Lazarova、Sami S. Zoghbi、Jinsoo Hong、Nicholas Seneca、Ed Tuan、Robert L. Gladding、Jeih-San Liow、Andrew Taku、Robert B. Innis、Victor W. Pike

  DOI：10.1021/jm800510m

  日期：2008.10.9

  [C-11]Loperamide has been proposed for imaging P-glycoprotein (P-gp) function with positron emission tomography (PET), but its metabolism to [N-methyl-C-11]N-desmethyl-loperamide ([C-11]dLop; [C-11]3) precludes quantification. We considered that [C-11]3 might itself be a superior radiotracer for imaging brain P-gp function and therefore aimed to prepare [C-11]3 and characterize its efficacy. An amide precursor (2) was synthesized and methylated with [C-11]iodomethane to give [C-11]3. After administration of [C-11]3 to wild-type mice, brain radioactivity uptake was very low. In P-gp (mdr-la(-/-)) knockout mice, brain uptake of radioactivity at 30 min increased about 3.5-fold by PET measures, and over 7-fold by ex vivo measures. In knockout mice, brain radioactivity was predominantly (90%) unchanged radiotracer. In monkey PET experiments, brain radioactivity uptake was also very low but after P-gp blockade increased more than 7-fold. [C-11]3 is an effective new radiotracer for imaging brain P-gp function and, in favor of future successful quantification, appears free of extensive brain-penetrant radiometabolites.
• Radiotracers for imaging P-glycoprotein function
  申请人：National Institutes of Health Represented by the Secretary of the Department of Health and Human Services, National Institutes of Health

  公开号：US07989630B2

  公开（公告）日：2011-08-02

  P-glycoprotein transporter (P-gp) acts as a pump at the blood-brain barrier to exclude a wide range of xenobiotics (e.g., toxins, drugs, etc.) from the brain and is also expressed in a tumor in response to exposure to established or prospective chemotherapeutics (a phenomenon known as multidrug resistance). This invention concerns the preparation and use of radiotracers for imaging P-gp function in vitro and in vivo. Radiotracers of the present invention are avid substrates for P-gp and have structures based on N-Desmethyl-loperamide.

  P-糖蛋白转运体（P-gp）在血脑屏障上起泵的作用，排除各种异物（如毒素、药物等）进入大脑，并且在肿瘤中表达，以应对已知或可能的化疗药物（这种现象称为多药耐药）。本发明涉及制备和使用放射示踪剂来体外和体内成像P-gp功能。本发明的放射示踪剂是P-gp的亲和底物，并且基于N-去甲基-洛哌丁的结构。