isopropyl 3-{3-[2-(dimethylamino)ethoxy]benzoyl}-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 3-{3-[2-(dimethylamino)ethoxy]benzoyl}-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
• 英文别名: 1-methylethyl 3-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)carbonyl]-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate；propan-2-yl 3-[3-[2-(dimethylamino)ethoxy]benzoyl]-1,1-dimethyl-2,6-dihydroazepino[4,5-b]indole-5-carboxylate
• 化学式: C₂₉H₃₅N₃O₄
• 分子量: 489.615
• InChiKey: QIWSBARWQJTSAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  isopropyl 3-(3-hydroxybenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 、 N,N-二甲基乙醇胺 在 三苯基膦树脂 、 偶氮二甲酸二异丙酯 作用下， 以 四氢呋喃 为溶剂， 以15%的产率得到isopropyl 3-{3-[2-(dimethylamino)ethoxy]benzoyl}-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
  参考文献：
  名称：

  WO2007/70796

  摘要：

  公开号：

文献信息

• 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。
• Improvement of Physiochemical Properties of the Tetrahydroazepinoindole Series of Farnesoid X Receptor (FXR) Agonists: Beneficial Modulation of Lipids in Primates
  作者：Joseph T. Lundquist、Douglas C. Harnish、Callain Y. Kim、John F. Mehlmann、Rayomand J. Unwalla、Kristin M. Phipps、Matthew L. Crawley、Thomas Commons、Daniel M. Green、Weixin Xu、Wah-Tung Hum、Julius E. Eta、Irene Feingold、Vikram Patel、Mark J. Evans、KehDih Lai、Lisa Borges-Marcucci、Paige E. Mahaney、Jay E. Wrobel

  DOI：10.1021/jm901650u

  日期：2010.2.25

  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.
• AZEPINOINDOLE DERIVATIVES AS PHARMACEUTICAL AGENTS
  申请人：Exelixis, Inc.

  公开号：EP1963331A1

  公开（公告）日：2008-09-03
• [EN] AZEPINOINDOLE DERIVATIVES AS PHARMACEUTICAL AGENTS<br/>[FR] DERIVES D'AZEPINOINDOLE EN TANT QU'AGENTS PHARMACEUTIQUES
  申请人：EXELIXIS INC

  公开号：WO2007070796A1

  公开（公告）日：2007-06-21

  [EN] The present invention relates to compounds of formula I, which exhibit affinity for the farnesoid X receptor.
  [FR] La présente invention concerne des composés, des compositions et des procédés destinés à moduler l'activité de récepteurs. L'invention concerne en particulier des composés et des compositions destinés à moduler l'activité de récepteurs et à traiter, à prévenir ou à améliorer un ou plusieurs symptômes de maladie ou de trouble directement ou indirectement liés à l'activité des récepteurs.