(+/-)-{4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl}[2-(3-hydroxybutyl)benzofuran-3-yl]methanone | 725684-62-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (+/-)-{4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl}[2-(3-hydroxybutyl)benzofuran-3-yl]methanone
• 英文别名: 3-hydroxy amiodarone；Amiodarone metabolite M11-2；[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]-[2-(3-hydroxybutyl)-1-benzofuran-3-yl]methanone
• CAS: 725684-62-8
• 化学式: C₂₅H₂₉I₂NO₄
• 分子量: 661.319
• InChiKey: IIOUFGJTYMDOPR-UHFFFAOYSA-N

物化性质

• 沸点：
  670.3±55.0 °C(Predicted)
• 密度：
  1.628±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  62.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  胺碘酮 在 CYP₂J₂ recombinant enzyme 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 为溶剂， 反应 1.0h， 生成 (+/-)-{4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl}[2-(3-hydroxybutyl)benzofuran-3-yl]methanone
  参考文献：
  名称：

  Using pure shift HSQC to characterize microgram samples of drug metabolites

  摘要：

  Difficulties in isolating samples from complex biological matrices and sensitivity limitations have long stymied the utilization of heteronuclear 2D NMR for the characterization of drug metabolites. Small diameter cryogenic NMR probes have largely ameliorated sensitivity limitations and the recently reported pure shift HSQC 2D NMR pulse sequence offers a further and marked improvement in both resolution and sensitivity. Using a 7.4 mu g sample of the commercially available metabolite 3-hydroxy carbamazepine dissolved in 30 mu L of deuterated solvent and a 600 MHz NMR equipped with a 1.7 mm cryogenic NMR probe, it was possible to acquire high signal-to-noise pure shift HSQC data in just over 30 min. A conventional HSQC spectrum acquired with identical parameters had approximately half the signal-to-noise of the pure shift HSQC spectrum. Collapsing the vicinal homonuclear couplings in the pure shift HSQC spectrum also significantly improves resolution. A practical, real world application of the technique is illustrated with the chromatographically isolated metabolite 3-hydroxy amiodarone from incubation with CYP2J2 recombinant enzyme. High quality pure shift HSQC data were recorded in slightly over 14 h for a 3 mu g sample of the metabolite. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.06.067

文献信息

• ——
  作者：Barbara Wendt、Huy Riem Ha、Manfred Hesse

  DOI：10.1002/1522-2675(200209)85:9<2990::aid-hlca2990>3.0.co;2-r

  日期：2002.9

  The metabolism of the potent antiarrythmic drug amiodarone (AMI 1) has yet not been fully investigated. Recently, in vitro experiments revealed that in rabbit-liver microsomes, AMI (1) and its main metabolite MDEA (2) were biotransformed to the hydroxylated derivatives T-OH-AMI (3) and 3'-OH-MDEA (4). respectively. To establish the chemical structure of 3 and 4, we developed a total synthesis of these two metabolites of AMI (1). H-1- and C-13-NMR Signal assignment from HSQC and HMBC 2D NMR data of synthesized 4 showed that the proposed structure of metabolite 4 is correct. Even the structure of 3 was found to be correct by comparing its HPLC/MS-MS/MS with the data described earlier.