异丙基(10,11-二氢-5H-二苯并[B,F]吖庚英-3-基)氨基甲酯 | 78816-59-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 异丙基(10,11-二氢-5H-二苯并[B,F]吖庚英-3-基)氨基甲酯
• 英文名称: isopropyl (10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)carbamate
• 英文别名: propan-2-yl N-(6,11-dihydro-5H-benzo[b][1]benzazepin-2-yl)carbamate
• CAS: 78816-59-8
• 化学式: C₁₈H₂₀N₂O₂
• mdl: MFCD00560891
• 分子量: 296.369
• InChiKey: YJXOMYBLVRMVSB-UHFFFAOYSA-N

物化性质

• 熔点：
  146-148 °C(Solv: isopropanol (67-63-0))
• 沸点：
  394.2±42.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  异丙基(10,11-二氢-5H-二苯并[B,F]吖庚英-3-基)氨基甲酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.0h， 生成 isopropyl (5-(2-(1H-pyrrol-1-yl)acetyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)carbamate
  参考文献：
  名称：

  [EN] SELECTIVE INHIBITORS OF CONSTITUTIVE ANDROSTANE RECEPTOR
  [FR] INHIBITEURS SÉLECTIFS DU RÉCEPTEUR CONSTITUTIF DES ANDROSTANES

  摘要：

  本发明的化合物是CAR的拮抗剂，对CAR的特异性高于其他蛋白，包括PXR。所披露的化合物可用于治疗或控制细胞增殖障碍，特别是肿瘤学疾病，例如癌症。本摘要旨在作为特定技术领域搜索的扫描工具，并不是要限制本发明。

  公开号：

  WO2016064682A1
• 作为产物：
  描述：

  亚氨基二苄 在 盐酸 、 硫酸 、 palladium on activated charcoal 、 氢气 、 硝酸 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 5.83h， 生成 异丙基(10,11-二氢-5H-二苯并[B,F]吖庚英-3-基)氨基甲酯
  参考文献：
  名称：

  [EN] SELECTIVE INHIBITORS OF CONSTITUTIVE ANDROSTANE RECEPTOR
  [FR] INHIBITEURS SÉLECTIFS DU RÉCEPTEUR CONSTITUTIF DES ANDROSTANES

  摘要：

  本发明的化合物是CAR的拮抗剂，对CAR的特异性高于其他蛋白，包括PXR。所披露的化合物可用于治疗或控制细胞增殖障碍，特别是肿瘤学疾病，例如癌症。本摘要旨在作为特定技术领域搜索的扫描工具，并不是要限制本发明。

  公开号：

  WO2016064682A1

文献信息

• Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor
  作者：Wenwei Lin、Lei Yang、Sergio C. Chai、Yan Lu、Taosheng Chen

  DOI：10.1016/j.ejmech.2015.12.018

  日期：2016.1

  Constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) are master regulators of endobiotic and xenobiotic metabolism and disposition. Because CAR is constitutively active in certain cellular contexts, inhibiting CAR might reduce drug-induced hepatotoxicity and resensitize drug resistant cancer cells to chemotherapeutic drugs. We recently reported a novel CAR inhibitor/inverse agonist CINPA1 (11). Here, we have obtained or designed 54 analogs of CINPA1 and used a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate their CAR inhibition potency. Many of the 54 analogs showed CAR inverse agonistic activities higher than those of CINPA1, which has an IC50 value of 687 nM. Among them, 72 has an IC50 value of 11.7 nM, which is about 59-fold more potent than CINPA1 and over 10-fold more potent than clotrimazole (an IC50 value of 126.9 nM), the most potent CAR inverse agonist in a biochemical assay previously reported by others. Docking studies provide a molecular explanation of the structure activity relationship (SAR) observed experimentally. To our knowledge, this effort is the first chemistry endeavor in designing and identifying potent CAR inverse agonists based on a novel chemical scaffold, leading to 72 as the most potent CAR inverse agonist so far. The 54 chemicals presented are novel and unique tools for characterizing CAR's function, and the SAR information gained from these 54 analogs could guide future efforts to develop improved CAR inverse agonists. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Wunderlich; Stark; Carstens, Pharmazie, 1985, vol. 40, # 12, p. 827 - 830
  作者：Wunderlich、Stark、Carstens、Lohmann、Grizenko、Skoldinov

  DOI：——

  日期：——
• 3-Alkoxycarbonylamino-5-acylaminoiminodibenzyls and their antiarrhythmic activity
  作者：A. P. Skoldinov、N. V. Kaverina、A. N. Gritsenko、V. V. Lyskovtsev、A. I. Turilova、H. Wunderlich、A. Stark、H. Poppe、R. Barch、L. Zenker、D. Loman

  DOI：10.1007/bf02219697

  日期：1996.3
• WUNDERLICH, H.;STARK, A.;CARSTENS, E.;LOHMANN, D.;GRIZENKO, A. N.;SKOLDIN+, PHARMAZIE, 1985, 40, N 12, 827-830
  作者：WUNDERLICH, H.、STARK, A.、CARSTENS, E.、LOHMANN, D.、GRIZENKO, A. N.、SKOLDIN+

  DOI：——

  日期：——
• SELECTIVE INHIBITORS OF CONSTITUTIVE ANDROSTANE RECEPTOR
  申请人：ST. JUDE CHILDREN'S RESEARCH HOSPITAL

  公开号：US20170226115A1

  公开（公告）日：2017-08-10

  The compounds of the invention are antagonists of CAR, with specificity for CAR over other proteins including PXR. The disclosed compounds are useful in treating or controlling cell proliferative disorders, in particular oncological disorders, such as cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.