isopropyl 1,1-dimethyl-3-{4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate | 1207988-07-5

• 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 1,1-dimethyl-3-{4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
• 英文别名: Isopropyl 1,1-Dimethyl-3-{4-[2-(4-methylpiperazin-1-yl)ethoxy]-benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate；propan-2-yl 1,1-dimethyl-3-[4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl]-2,6-dihydroazepino[4,5-b]indole-5-carboxylate
• CAS: 1207988-07-5
• 化学式: C₃₂H₄₀N₄O₄
• 分子量: 544.694
• InChiKey: UFOOUSROGOQPAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  78.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 、 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-(4-methylpiperazin-1-yl)ethoxy]benzoyl}-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
• 作为试剂：
  描述：

  isopropyl 3-[4-(2-bromoethoxy)benzoyl]-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 、 N-甲基哌嗪 、 三乙胺 、 甲醇 在 甲醇 、 水 、 acetonitrile-water 、 乙腈 、 isopropyl 1,1-dimethyl-3-{4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 18.27h， 以to give the titled compound, isopropyl 1,1-dimethyl-3-{4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate的产率得到isopropyl 1,1-dimethyl-3-{4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
  参考文献：
  名称：

  1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate nuclear receptor inhibitors

  摘要：

  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。

  公开号：

  US20110039824A1

文献信息

• 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.