isopropyl 3-[4-(2-bromoethoxy)benzoyl]-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate | 1207988-23-5

• 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
• 英文名称: isopropyl 3-[4-(2-bromoethoxy)benzoyl]-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
• 英文别名: propan-2-yl 3-[4-(2-bromoethoxy)benzoyl]-1,1-dimethyl-2,6-dihydroazepino[4,5-b]indole-5-carboxylate
• CAS: 1207988-23-5
• 化学式: C₂₇H₂₉BrN₂O₄
• 分子量: 525.442
• InChiKey: XSRBAJOBGRLVNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 isopropyl 3-[4-(2-bromoethoxy)benzoyl]-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 以 N-甲基吡咯烷酮 为溶剂， 反应 18.0h， 生成 isopropyl 1,1-dimethyl-3-[4-(2-pyrrolidin-1-ylethoxy)benzoyl]-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
  参考文献：
  名称：

  Improvement of Physiochemical Properties of the Tetrahydroazepinoindole Series of Farnesoid X Receptor (FXR) Agonists: Beneficial Modulation of Lipids in Primates

  摘要：

  In an effort to develop orally active farnesoid X receptor (FXR) agonists, a series of tetrahydroazepinoindoles with appended solubilizing amine functionalities were synthesized. The crystal structure of the previously disclosed FXR agonist, 1 (FXR-450), aided in the design of compounds with tethered solubilizing functionalities designed to reach the solvent cavity around the hFXR receptor. These compounds were soluble in 0.5% methylcellulose/2% Tween-80 in water (MC/T) for oral administration. In vitro and in vivo optimization led to the identification of 14dd and 14cc, which in a dose-dependent fashion regulated low density lipoprotein cholesterol (LDLc) in low density lipoprotein receptor knockout (LDLR-/-) mice. Compound 14cc was dosed in female rhesus monkeys for 4 weeks at 60 mg/kg daily in MC/T vehicle. After 7 days, triglyceride (TG) levels and very low density lipoprotein cholesterol (VLDLc) levels were significantly decreased and LDLc was decreased 63%. These data are the first to demonstrate the dramatic lowering of serum LDLc levels by a FXR agonist in primates and supports the potential utility of 14cc in treating dyslipidemia in humans beyond just TG lowering.

  DOI：

  10.1021/jm901650u
• 作为产物：
  描述：

  isopropyl 3-(4-hydroxybenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 、 2-溴乙醇 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 isopropyl 3-[4-(2-bromoethoxy)benzoyl]-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
  参考文献：
  名称：

  [EN] 1,2,3,6-TETRAHYDROAZEPINO[4,5-B]INDOLE-5-CARBOXYLATE NUCLEAR RECEPTOR INHIBITORS
  [FR] INHIBITEURS DES RÉCEPTEURS NUCLÉAIRES DE 1,2,3,6-TÉTRAHYDROAZÉPINO[4,5-B]INDOLE-5-CARBOXYLATE

  摘要：

  提供了一些1,2,3,6-四氢噁二氮杂并[4,5-b]吲哚-5-羧酸酯化合物，这些化合物对调节核受体的活性（如法尼索X受体）非常有用，或者用于治疗、预防或改善与这些受体活性相关的疾病或疾病。

  公开号：

  WO2010036362A1

文献信息

• 1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate nuclear receptor inhibitors
  申请人：Lundquist, IV Joseph Theodore

  公开号：US20110039824A1

  公开（公告）日：2011-02-17

  Provided are certain 1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate compounds which are useful for modulating the activity of nuclear receptors, such as farnesoid X receptors, and/or for the treatment, prevention, or amelioration diseases or disorders related to the activity of these receptors.

  提供了某些1,2,3,6-四氢-氮杂二环[4,5-b]吲哚-5-羧酸酯化合物，这些化合物对调节核受体（如法尼酰丙二酸X受体）的活性，以及治疗、预防或改善与这些受体活性相关的疾病或紊乱非常有用。
• 1,2,3,6-TETRAHYDROAZEPINO[4,5-B]INDOLE-5-CARBOXYLATE NUCLEAR RECEPTOR INHIBITORS
  申请人：Wyeth LLC

  公开号：EP2334681A1

  公开（公告）日：2011-06-22