3-(2-{[3-(9H-咔唑-4-基氧基)-2-羟基丙基]氨基}乙氧基)-4-甲氧基苯酚 | 142227-51-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 3-(2-{[3-(9H-咔唑-4-基氧基)-2-羟基丙基]氨基}乙氧基)-4-甲氧基苯酚
• 中文别名: 5'-羟基苯基卡维地洛；5'-羟苯基卡维地洛
• 英文名称: 5'-Hydroxyphenyl carvedilol
• 英文别名: (2RS)-1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxy-5-hydroxyphenoxy)ethyl]amino]propan-2-ol；1-[9H-carbazol-4-yloxy]-3-[[2-(5-hydroxy-2-methoxyphenoxy)ethyl]amino]-2-propanol；5'-hydroxycarvedilol；4'-hydroxycarvedilol；3-[2-[[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]amino]ethoxy]-4-methoxyphenol
• CAS: 142227-51-8
• 化学式: C₂₄H₂₆N₂O₅
• 分子量: 422.481
• InChiKey: PVUVZUBTCLBJMT-UHFFFAOYSA-N

物化性质

• 熔点：
  >182°C (dec.)
• 沸点：
  702.0±60.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  96
• 氢给体数：
  4
• 氢受体数：
  6

安全信息

• 储存条件：
  -20°C，密闭保存，并保持干燥。

制备方法与用途

5'-羟基苯卡维拉是卡维地洛的代谢产物，用于治疗高血压。

反应信息

• 作为产物：
  描述：

  4-羟基咔唑 在 lithium bromide 作用下， 以 异丙醇 为溶剂， 反应 12.0h， 生成 3-(2-{[3-(9H-咔唑-4-基氧基)-2-羟基丙基]氨基}乙氧基)-4-甲氧基苯酚
  参考文献：
  名称：

  Suppression of store overload-induced calcium release by hydroxylated metabolites of carvedilol

  摘要：

  Carvedilol is a drug widely used in the treatment of heart failure and associated cardiac arrhythmias. A unique action of carvedilol is its suppression of store overload-induced calcium release (SOICR) through the cardiac ryanodine receptor (RyR2), which can trigger ventricular arrhythmias. Since the effects of carvedilol metabolites on SOICR have not yet been investigated, three carvedilol metabolites hydroxylated at the 3-, 4' and 5'-positions were synthesized and assayed for SOICR inhibition in mutant HEK 293 cells expressing the RyR2 mutant R4496C. This cell line is especially prone to SOICR and calcium release through the defective RyR2 channel was measured with a calcium-sensitive fluorescent dye. These results revealed that the 3- and 4'-hydroxy derivatives are slightly more effective than carvedilol in suppressing SOICR, while the 5'-analog proved slightly less active. Metabolic deactivation of carvedilol via these hydroxylation pathways is therefore insignificant. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.008

文献信息

• Synthesis of Active Metabolites of Carvedilol, an Antihypertensive Drug
  作者：N. Senthilkumar、Y. S. Somannavar、Shankar B. Reddy、Brajesh Kumar Sinha、G. K. A. S. S. Narayan、Ramesh Dandala、Kaga Mukkanti

  DOI：10.1080/00397910903534072

  日期：2010.12.22

  A simple synthetic route for active metabolites of carvedilol is reported. The metabolites 4'-hydroxycarvedilol and 5'-hydroxycarvedilol have exhibited high activity for -blockade. We have disclosed syntheses of 4'-hydroxycarvedilol and 5'-hydroxycarvedilol from commercially available vanillin and isovanillin, respectively.
• Suppression of store overload-induced calcium release by hydroxylated metabolites of carvedilol
  作者：Thomas Malig、Zhichao Xiao、S.R. Wayne Chen、Thomas G. Back

  DOI：10.1016/j.bmcl.2015.11.008

  日期：2016.1

  Carvedilol is a drug widely used in the treatment of heart failure and associated cardiac arrhythmias. A unique action of carvedilol is its suppression of store overload-induced calcium release (SOICR) through the cardiac ryanodine receptor (RyR2), which can trigger ventricular arrhythmias. Since the effects of carvedilol metabolites on SOICR have not yet been investigated, three carvedilol metabolites hydroxylated at the 3-, 4' and 5'-positions were synthesized and assayed for SOICR inhibition in mutant HEK 293 cells expressing the RyR2 mutant R4496C. This cell line is especially prone to SOICR and calcium release through the defective RyR2 channel was measured with a calcium-sensitive fluorescent dye. These results revealed that the 3- and 4'-hydroxy derivatives are slightly more effective than carvedilol in suppressing SOICR, while the 5'-analog proved slightly less active. Metabolic deactivation of carvedilol via these hydroxylation pathways is therefore insignificant. (C) 2015 Elsevier Ltd. All rights reserved.