isopropyl 8-fluoro-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate

• 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 8-fluoro-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
• 英文别名: Azepino[4,5-b]indole-5-carboxylic acid, 8-fluoro-1,2,3,6-tetrahydro-1,1-dimethyl-, 1-methylethyl ester；propan-2-yl 8-fluoro-1,1-dimethyl-3,6-dihydro-2H-azepino[4,5-b]indole-5-carboxylate
• 化学式: C₁₈H₂₁FN₂O₂
• 分子量: 316.375
• InChiKey: LCBILDCOUYKCBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  isopropyl 8-fluoro-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 、 4-氯甲基苯甲酰氯 在 三乙胺 作用下， 以 乙腈 为溶剂， 生成 isopropyl 3-[4-(chloromethyl)benzoyl]-8-fluoro-1,1-dimethyl-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：

  3-溴-2-氧代丙酸异丙酯 、 2-(6-fluoro-1H-indol-3-yl)-2-methylpropan-1-amine hydrochloride 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 异丙醇 、 乙腈 为溶剂， 生成 isopropyl 8-fluoro-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

• [EN] FUSED BICYCLIC COMPOUNDS FOR THE TREATMENT OF DISEASE<br/>[FR] COMPOSÉS BICYCLIQUES FUSIONNÉS POUR LE TRAITEMENT DE MALADIES
  申请人：AKARNA THERAPEUTICS LTD

  公开号：WO2016151403A1

  公开（公告）日：2016-09-29

  Described herein are fused bicyclic compounds, compositions, and methods for their use for the treatment of disease.

  本文描述了融合的双环化合物、组合物以及它们用于治疗疾病的方法。
• Azepinoindole Derivatives As Pharmaceutical Agents
  申请人：Baik Tae-Gon

  公开号：US20090203577A1

  公开（公告）日：2009-08-13

  The present invention relates to compounds of formula I, which exhibit affinity for the farnesoid X receptor.

  本发明涉及I式化合物，该化合物具有与法尼索X受体的亲和力。
• 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。
• FUSED BICYCLIC COMPOUNDS FOR THE TREATMENT OF DISEASE
  申请人：Akarna Therapeutics, Ltd.

  公开号：EP3715348A1

  公开（公告）日：2020-09-30

  Described herein are fused bicyclic compounds, compositions, and methods for their use for the treatment of disease.

  本文描述了融合双环化合物、组合物及其用于治疗疾病的方法。
• Fused bicyclic compounds for the treatment of disease
  申请人：AKARNA THERAPEUTICS, LTD.

  公开号：US10421759B2

  公开（公告）日：2019-09-24

  Described herein are fused bicyclic compounds, compositions, and methods for their use for the treatment of disease.

  本文描述了融合双环化合物、组合物及其用于治疗疾病的方法。