甲酮,(2-丁基-3-苯并呋喃基)[4-(2-羟基乙氧基)-3,5-二碘苯基]- | 135048-44-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 甲酮,(2-丁基-3-苯并呋喃基)[4-(2-羟基乙氧基)-3,5-二碘苯基]-
• 英文名称: (2-butylbenzofuran-3-yl)-[4-(2-hydroxyethoxy)-3,5-diiodophenyl]-methanone
• 英文别名: (2-butylbenzofuran-3-yl)-[4-(2-hydroxyethoxy)-3,5-diiodophenyl]methanone；2-n-butyl-3-(3,5-diiodo-4-ω-hydroxyethoxybenzoyl)-benzofuran；2-n-butyl-3-(3,5-diiodo-4-β-hydroxyethoxybenzoyl)benzofuran；Amiodarone metabolite M5；(2-butyl-1-benzofuran-3-yl)-[4-(2-hydroxyethoxy)-3,5-diiodophenyl]methanone
• CAS: 135048-44-1
• 化学式: C₂₁H₂₀I₂O₄
• 分子量: 590.196
• InChiKey: FHWJUIZOKDUAQQ-UHFFFAOYSA-N

物化性质

• 熔点：
  69.6-72.9 °C
• 沸点：
  639.5±55.0 °C(Predicted)
• 密度：
  1.775±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 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：
  59.7
• 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 、 碘酸 作用下， 以 溶剂黄146 为溶剂， 生成 甲酮,(2-丁基-3-苯并呋喃基)[4-(2-羟基乙氧基)-3,5-二碘苯基]-
  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

• Hepatocellular Toxicity and Pharmacological Effect of Amiodarone and Amiodarone Derivatives
  作者：Katri Maria Waldhauser、Michael Török、Huy-Riem Ha、Urs Thomet、Daniel Konrad、Karin Brecht、Ferenc Follath、Stephan Krähenbühl

  DOI：10.1124/jpet.106.108993

  日期：2006.12

  and annexin V/propidium iodide staining. The effect of the three least toxic amiodarone analogs on the human ether-a-go-go-related gene (hERG) channel was compared with amiodarone. Amiodarone, B2-O-acetate, and B2-O-Et-N-dipropyl (each 10 microM) significantly reduced the hERG tail current amplitude, whereas 10 microM B2-O-Et displayed no detectable effect on hERG outward potassium currents. In conclusion

  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
• 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.
• COMPOSITIONS AND METHODS FOR TREATING ATRIAL FIBRILLATION
  申请人：Edge Therapeutics, Inc.

  公开号：US20180055813A1

  公开（公告）日：2018-03-01

  The described invention provides delivery systems, compositions and methods for reducing incidence or severity of atrial fibrillation in a subject at risk thereof, the method comprising providing a delivery system in a form that is malleable comprising a particulate formulation containing a plurality of particles comprising a therapeutic amount of an anti-arrhythmic agent; and a pharmaceutically acceptable carrier, wherein the therapeutic amount of the therapeutic agent is effective to reduce the incidence or severity of atrial fibrillation.
• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210228723A1

  公开（公告）日：2021-07-29

  The present disclosure relates to compounds and methods which may be useful for modulating the expression of fxn and treating diseases and conditions in which fxn plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence GAA; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence GAA; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.