isopropyl 3-(3-(chloromethyl)benzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate | 942146-33-0

• 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-(3-(chloromethyl)benzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
• 英文别名: 1-methylethyl 3-{[3-(chloromethyl)phenyl]carbonyl}-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate；propan-2-yl 3-[3-(chloromethyl)benzoyl]-1,1-dimethyl-2,6-dihydroazepino[4,5-b]indole-5-carboxylate
• CAS: 942146-33-0
• 化学式: C₂₆H₂₇ClN₂O₃
• 分子量: 450.965
• InChiKey: PLFXCTJJTONANA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  62.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  isopropyl 3-(3-(chloromethyl)benzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 、 N-Boc-哌嗪 在 N,N-二异丙基乙胺 、 盐酸 作用下， 以 1,2-二氯乙烷 、 1,4-二氧六环 、 丙酮 为溶剂， 反应 2.0h， 以98%的产率得到1-methylethyl 1,1-dimethyl-3-{[3-(piperazin-1-ylmethyl)phenyl]carbonyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate hydrochloride
  参考文献：
  名称：

  WO2007/70796

  摘要：

  公开号：
• 作为产物：
  描述：

  1,2,3,6-四氢-1,1-二甲基-氮杂卓酮[4,5-B]吲哚-5-羧酸-1-甲基乙酯 、 3-(氯甲基)苯甲酰氯 在 三乙胺 作用下， 以 乙腈 为溶剂， 生成 isopropyl 3-(3-(chloromethyl)benzoyl)-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

文献信息

• [EN] 1,2,3,6-TETRAHYDROAZEPINO[4,5-B]INDOLE-5-CARBOXYLATE NUCLEAR RECEPTOR INHIBITORS<br/>[FR] INHIBITEURS DES RÉCEPTEURS NUCLÉAIRES DE 1,2,3,6-TÉTRAHYDROAZÉPINO[4,5-B]INDOLE-5-CARBOXYLATE
  申请人：WYETH CORP

  公开号：WO2010036362A1

  公开（公告）日：2010-04-01

  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。
• 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。
• 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