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 | 942145-77-9

• 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
• 中文名称: 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
• 英文名称: isopropyl 1,1-dimethyl-1,2,3,6-tetrahydro-azepino[4,5-b]indole-5-carboxylate
• 英文别名: Isopropyl 1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate；propan-2-yl 1,1-dimethyl-3,6-dihydro-2H-azepino[4,5-b]indole-5-carboxylate
• CAS: 942145-77-9
• 化学式: C₁₈H₂₂N₂O₂
• 分子量: 298.385
• InChiKey: LWOPKUFMTHTYQL-UHFFFAOYSA-N

物化性质

• 沸点：
  492.3±45.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 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：
  3

安全信息

• 海关编码：
  2933990090
• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  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 在 N,N-二甲基甲酰胺 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 isopropyl 3-[4-(benzyloxy)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：
• 作为产物：
  描述：

  isopropyl 1-(bromomethyl)-4,4-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylate 以40的产率得到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
  参考文献：
  名称：

  J. Med. Chem. 2009, 52, 904-907

  摘要：

  DOI：

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。
• Discovery of XL335 (WAY-362450), a Highly Potent, Selective, and Orally Active Agonist of the Farnesoid X Receptor (FXR)
  作者：Brenton Flatt、Richard Martin、Tie-Lin Wang、Paige Mahaney、Brett Murphy、Xiao-Hui Gu、Paul Foster、Jiali Li、Parinaz Pircher、Mary Petrowski、Ira Schulman、Stefan Westin、Jay Wrobel、Grace Yan、Eric Bischoff、Chris Daige、Raju Mohan

  DOI：10.1021/jm8014124

  日期：2009.2.26

  Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X receptor (FXR). In vitro and in vivo optimization has led to the discovery of 6m (XL335, WAY-362450) as a potent, selective, and orally bioavailable FXR agonist (EC(50) = 4 nM, Eff = 149%). Oral administration of 6m to LDLR(-/-) mice results in lowering of cholesterol and triglycerides. Chronic administration in an atherosclerosis model results in significant reduction in aortic arch lesions.
• 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.