3-羟基卡维地洛 | 146574-43-8

• 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-羟基卡维地洛
• 英文名称: 1-[3-hydroxycarbazolyl-(4)-oxy]-3-[2-(2-methoxyphenoxy)ethylamino]propanol-(2)
• 英文别名: 1-[3-hydroxycarbazolyl-(4)-oxy]-3-[(2-methoxyphenoxyethyl)amino]-propanol-(2)；4-[2-hydroxyl-3-[[2(2-methoxy-phenoxy)ethyl]amino]propoxyl]-9H-carbazol-3-ol；1-[3-hydroxycarbazol-4-yloxy]-3-[(2-methoxyphenoxyethyl)amino]propan-2-ol；3-hydroxycarvedilol；BM 91.0228；BM 910228；3-Hydroxy Carvedilol；4-[2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]propoxy]-9H-carbazol-3-ol
• CAS: 146574-43-8
• 化学式: C₂₄H₂₆N₂O₅
• 分子量: 422.481
• InChiKey: RWDSIYCVHJZURY-UHFFFAOYSA-N

物化性质

• 沸点：
  702.0±60.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)
• 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)：
  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

反应信息

• 作为产物：
  描述：

  4-羟基咔唑 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 22.0h， 生成 3-羟基卡维地洛
  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

• [EN] MEDICAMENT FOR PREVENTIVE AND THERAPEUTIC TREATMENT OF INFLAMMATORY DISEASES<br/>[FR] MEDICAMENT POUR LA PROPHYLAXIE ET LE TRAITEMENT DES MALADIES INFLAMMATOIRES
  申请人：——

  公开号：WO1998038985A2

  公开（公告）日：1998-09-11

  [EN] Medicament for preventive and therapeutic treatment of inflammatory diseases which comprises as an active ingredient a substance selected from the group consisting of carvedilol, optically active isomers thereof, its hydroxy-carbazole derivatives and pharmacologically acceptable salts thereof.
  [FR] L'invention a pour objet un médicament pour la prophylaxie et le traitement des maladies inflammatoires. Ce médicament comprend un ingrédient actif comme substance choisie dans le groupe se composant de carvedilol, d'isomères de ce dernier, actifs sur le plan optique, de ses dérivés hydroxy-carbazole et de sels pharmacologiquement acceptables de ces derniers.
• [EN] MEDICAMENT FOR PREVENTIVE AND THERAPEUTIC TREATMENT OF VIRAL INFECTIONS<br/>[FR] MEDICAMENT POUR LA PREVENTION ET LA THERAPIE D'INFECTIONS VIRALES
  申请人：——

  公开号：WO1998038986A2

  公开（公告）日：1998-09-11

  [EN] Medicament for preventive and therapeutic treatment of viral infections which comprises as an active ingredient a substance selected from the group consisting of carvedilol, optically active isomers thereof, its hydroxy carbazole derivatives and pharmaceutically acceptable salts thereof.
  [FR] L'invention concerne un médicament pour la prévention et la thérapie d'infections virales. Ce médicament comprend un ingrédient actif comme substance choisie dans le groupe se composant de carvedilol, d'isomères de ce dernier, actifs sur le plan optique, de ses dérivés hydroxy-carbazole et de sels pharmacologiquement acceptables de ces derniers.
• 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.