di-N-desethylamiodarone hydrochloride | 757220-04-5

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: di-N-desethylamiodarone hydrochloride
• 英文别名: Di(N-desethyl) Amiodarone Hydrochloride；[4-(2-aminoethoxy)-3,5-diiodophenyl]-(2-butyl-1-benzofuran-3-yl)methanone;hydrochloride
• CAS: 757220-04-5
• 化学式: C₂₁H₂₁I₂NO₃*ClH
• 分子量: 625.673
• InChiKey: FTCJJBHXLGQNMI-UHFFFAOYSA-N

物化性质

• 熔点：
  189-190°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.97
• 重原子数：
  28
• 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：
  2
• 氢受体数：
  4

制备方法与用途

Di-N-desethyl Amiodarone hydrochloride 是胺碘酮（Amiodarone；HY-14187）的代谢产物，是一种强呼吸链抑制剂。胺碘酮则是一种抗心律失常药物，用于抑制 ATP 敏感性钾通道。

反应信息

• 作为产物：
  描述：

  2-丁基-3-(3,5-二碘-4-羟基苯甲酰)苯并呋喃 在 盐酸 作用下， 以 甲苯 为溶剂， 反应 4.5h， 生成 di-N-desethylamiodarone hydrochloride
  参考文献：
  名称：

  胺碘酮和胺碘酮衍生物的肝细胞毒性和药理作用。

  摘要：

  这项工作的目的是比较胺碘酮（2-正丁基-3- [3,5二碘-4--4-二乙基氨基乙氧基苯甲酰基]-苯并呋喃； B2-O-Et-N-二乙基）的肝细胞毒性和药理活性。胺碘酮衍生物。研究了三种胺碘酮代谢产物，即单-N-去乙基胺碘酮（B2-O-Et-NH-乙基），二-N-去乙基胺碘酮（B2-O-Et-NH（2））和（2-丁基-苯并呋喃带有乙醇侧链的（-3-基）-（4-羟基-3,5-二碘苯基）-甲酮（B2）[（2-丁基苯并呋喃-3-基）-[4-（2-羟基乙氧基）-3,5 -二碘苯基]-甲酮; B2-O-Et-OH]。另外，研究了五个胺碘酮类似物，即N-二甲基胺碘酮（B2-O-Et-N-二甲基），N-二丙基胺碘酮（B2-O-Et-N-二丙基），B2-O-携带乙酸酯侧链[[4-（2-丁基-苯并呋喃-3-羰基）-2,6-二碘代苯基]-乙酸; B2-O-乙酸盐]，带有丙酰胺侧链的B2-O-Et（B2-O-E-丙酰胺）和带有乙基侧链的B2-O

  DOI：

  10.1124/jpet.106.108993

文献信息

• Identification and quantitation of novel metabolites of amiodarone in plasma of treated patients
  作者：Huy Riem Ha、Laurent Bigler、Barbara Wendt、Marco Maggiorini、Ferenc Follath

  DOI：10.1016/j.ejps.2004.10.015

  日期：2005.3

  In mammals, mono-N-desethylamiodarone (MDEA) is the only known metabolite of amiodarone. Our previous experiments demonstrated that in vitro MDEA may be hydroxylated, N-dealkylated, and deaminated. In this report, we investigated the concentration of these microsomal metabolites in the plasma of patients receiving amiodarone. The presence of the hydroxy-amiodarone and deiodinated amiodarone was also additionally investigated. A high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry (HPLC-APCI-MS/MS) quantitative assay using morpholine-amiodarone as internal standard was developed for measuring these metabolites in the range of 3-250ng ml(-1). In the concentration ranges 5-50 and 50-250 ng ml(-1), the coefficients of variation of the measurements were less than 14 and 7%, respectively. The concentrations of investigated compounds in plasma of patients (n = 14) receiving amiodarone (0.2 g day (-1), orally for > 2 months) varied inter-individually and were 140.0 +/- 85.2, 39.1 +/- 20.8, and 26.2 +/- 15.2 ng ml(-1) for 3'OH-mono-N-desethylamiodarone, di-N-desethylamiodarone, and deaminated armodarone, respectively. The concentrations of MDEA and amiodarone in these samples were 970 +/- 347 and 11163 +/- 435 ng ml(-1), respectively. In contrast, the studied compounds were not detectable in plasma samples from eight patients receiving amiodarone intravenously. Qualitatively, in the plasma of patients receiving amiodarone orally, hydroxylated amiodarone was also positively detected by assaying the [M + Hj](+) ions at m/z 662, but the deiodo-metabolites of amiodarone were not detected using mass spectrometry. Thus, in humans, amiodarone and MDEA were biotransformed by dealkylation, hydroxylation, and deamination. (c) 2004 Elsevier B.V. All rights reserved.