二-N-去乙基胺碘酮 | 94317-95-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 二-N-去乙基胺碘酮
• 中文别名: 胺碘酮去二乙基杂质
• 英文名称: Didesethylamiodarone
• 英文别名: N,N-didesethylamiodarone；Di-desethylamiodarone；Di-N-desethylamiodarone；[4-(2-aminoethoxy)-3,5-diiodophenyl]-(2-butyl-1-benzofuran-3-yl)methanone
• CAS: 94317-95-0
• 化学式: C₂₁H₂₁I₂NO₃
• 分子量: 589.212
• InChiKey: ZOCLVGHDXBVATF-UHFFFAOYSA-N

物化性质

• 熔点：
  200.5-201.4 °C
• 沸点：
  629.0±55.0 °C(Predicted)
• 密度：
  1.740±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  27
• 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：

  2-丁基-3-(4-羟基苯甲酰基)苯并呋喃 在 碘 、 sodium ethanolate 、 碘酸 作用下， 以 溶剂黄146 为溶剂， 生成 二-N-去乙基胺碘酮
  参考文献：
  名称：

  胺碘酮类似物对甲状腺素碘化抑制作用的构效关系。

  摘要：

  目的胺碘酮（AMI）已被证明是一种有效的抗心律不齐化合物。由于AMI和甲状腺激素之间的结构相似性，该药物可能会抑制5'-甲状腺素-脱碘酶的活性。方法合成由（1）脱烷基，（2）脱碘和（3）脱氨基产生的AMI类似物，并将其用作甲状腺素（T4）到3,3'，5'-三碘甲腺氨酸（T3）的体外生物转化反应的抑制剂。使用高效液相色谱法和紫外检测法定量T3，发现I型5'-T4脱碘酶参与了该反应。在单独的场合，将AMI或A​​MI类似物作为抑制剂加入反应中。结果所有研究的AMI类似物均竞争性抑制5'-T4脱碘作用（Ki值范围为25-360 microM）。在1-1000 microM的浓度范围内，AMI及其N-去乙基，去碘化的类似物非常弱地抑制5'-T4的去碘化。在4-位带有羟基的AMI类似物是强抑制剂。而且，二碘代-AMI类似物比其相应的单碘或去碘代衍生物更强烈地抑制5'-T4去碘化。结论AMI的降解产物

  DOI：

  10.1007/s002280050701

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。
• Novel therapeutic agents for membrane transporters
  申请人：——

  公开号：US20030044845A1

  公开（公告）日：2003-03-06

  Novel multi-binding compounds (agents) are disclosed which bind cell membrane transporters including ion channels, molecular transporters and ion pumps. The compounds of this invention comprise from 2 to 10 ligands each of which can bind to such cellular transporters to modulate the biological processes/functions thereof. Each of the ligands is covalently attached to a linker (framework) to provide for a multi-binding compound. The linker is selected such that the multi-binding compound exhibits increased modulation of the biological processes/functions of the transporter as compared to the aggregate of the individual ligand units made available for binding to the transporter.

  本发明揭示了一种新型多重结合化合物（试剂），其结合细胞膜转运体，包括离子通道、分子转运体和离子泵。本发明的化合物包括2到10个配体，每个配体都可以结合到这些细胞转运体上，以调节其生物过程/功能。每个配体都共价地连接到一个连接器（框架）上，以提供多重结合化合物。所选择的连接器是为了使多重结合化合物相比可用于结合转运体的单个配体单元的聚合体表现出增强的调节转运体的生物过程/功能的特性。
• 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.
• NOVEL POTASSIUM CHANNEL DRUGS AND THEIR USES
  申请人：Advanced Medicine, Inc.

  公开号：EP1086063A1

  公开（公告）日：2001-03-28
• EP1089749A4
  申请人：——

  公开号：EP1089749A4

  公开（公告）日：2001-04-11