Didesethyl-deiodo-amiodarone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Didesethyl-deiodo-amiodarone
• 英文别名: [4-(2-amino-ethoxy)-3-iodo-phenyl]-(2-butyl-benzofuran-3-yl)-methanone；ddEdI-Ami；[4-(2-Aminoethoxy)-3-iodophenyl]-(2-butyl-1-benzofuran-3-yl)methanone
• 化学式: C₂₁H₂₂INO₃
• 分子量: 463.315
• InChiKey: SEMIZPFLBUWJCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  [4-(2-azido-ethoxy)-3-iodo-phenyl]-(2-butyl-benzofuran-3-yl)-methanone 在 三苯基膦 、 盐酸 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 4.0h， 以75%的产率得到Didesethyl-deiodo-amiodarone
  参考文献：
  名称：

  Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites

  摘要：

  Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites the iodothyronamines. Several of these amiodarone derivatives act as specific agonists of the G protein-coupled receptor (GPCR) trace amine-associated receptor 1 (TAAR(1)). This result demonstrates a novel molecular target for amiodarone derivatives with potential clinical significance. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.08.013

文献信息

• Quantification of Electrochemically Generated Iodine-Containing Metabolites Using Inductively Coupled Plasma Mass Spectrometry
  作者：Wiebke Lohmann、Björn Meermann、Ines Möller、Andy Scheffer、Uwe Karst

  DOI：10.1021/ac801878k

  日期：2008.12.15

  For the risk assessment of drug candidates, the identification and quantification of their metabolites is required. The majority of analytical techniques is based on calibration standards for quantification of the metabolites. As these often are not readily available, the use of inductively coupled plasma mass spectrometry (ICPMS) is an attractive alternative for drugs containing heteroatoms. In this work, the online coupling of electrochemistry (EC), liquid chromatography (LC), and ICPMS is presented. The antiarrhythmic agent amiodarone, which contains two iodine atoms, is oxidized in an electrochemical flow-through cell under N-dealkylation and deiodination. The metabolites that are generated at different EC potentials are identified by electrospray ionization (ESI) mass spectrometry, compared to those from rat liver microsomal incubations and quantified by ICPMS. Phase-optimized LC, a recent approach for high-performance isocratic separations, is used to avoid the ICPMS calibration problems known to occur with gradient separations. The potential of the complementary use of ESI-MS and ICPMS for the qualitative and quantitative analysis of drug metabolites becomes apparent in this work.

  为了对候选药物进行风险评估，需要鉴定和量化其代谢产物。大多数分析技术都是基于校准标准来量化代谢产物的。由于这些标准通常不易获得，因此对于含有杂原子的药物，使用电感耦合等离子体质谱（ICPMS）是一个有吸引力的替代方案。在这项工作中，我们介绍了电化学（EC）、液相色谱（LC）和ICPMS的在线耦合。抗心律失常药物胺碘酮含有两个碘原子，在N-脱烷基化和脱碘化的电化学流通池中氧化。通过电喷雾电离（ESI）质谱法鉴定在不同EC电位下产生的代谢产物，并与大鼠肝微粒体孵育产生的代谢产物进行比较，通过ICPMS进行量化。相位优化的LC是一种最近用于高效等度分离的方法，用于避免已知在梯度分离中出现的ICPMS校准问题。在这项工作中，ESI-MS和ICPMS互补用于药物代谢产物的定性和定量分析的潜力变得显而易见。
• Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites
  作者：Aaron N. Snead、Motonori Miyakawa、Edwin S. Tan、Thomas S. Scanlan

  DOI：10.1016/j.bmcl.2008.08.013

  日期：2008.11

  Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites the iodothyronamines. Several of these amiodarone derivatives act as specific agonists of the G protein-coupled receptor (GPCR) trace amine-associated receptor 1 (TAAR(1)). This result demonstrates a novel molecular target for amiodarone derivatives with potential clinical significance. (C) 2008 Elsevier Ltd. All rights reserved.