3-Carbethoxyamino-10,11-dihydro-5H-dibenzazepin | 78816-40-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 3-Carbethoxyamino-10,11-dihydro-5H-dibenzazepin
• 英文别名: 3-ethoxycarbonylamino-10,11-dihydro-5H-dibenz[b,f]azepine；3-carbethoxyamino-10,11-dihydro-5H-dibenzazepine；ethyl(10,11-dihydro-5h-dibenzo[b,f]azepin3-yl)carbamate；ethyl 10,11-dihydro-5H-dibenzo[b,f]azepin-3-ylcarbamate；ethyl N-(6,11-dihydro-5H-benzo[b][1]benzazepin-2-yl)carbamate
• CAS: 78816-40-7
• 化学式: C₁₇H₁₈N₂O₂
• mdl: MFCD00560904
• 分子量: 282.342
• InChiKey: DTRJAYJJIYBWRG-UHFFFAOYSA-N

物化性质

• 熔点：
  123-126 °C
• 沸点：
  385.6±42.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Carbethoxyamino-10,11-dihydro-5H-dibenzazepin 在 盐酸 、 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 乙醚 、 乙醇 、 水 为溶剂， 反应 11.0h， 生成 3-(N-methyl-N-ethoxycarbonyl)-10,11-dihydro-5H-dibenz[b,f]azepine
  参考文献：
  名称：

  3-Alkoxycarbonylamino-5-acylaminoiminodibenzyls and their antiarrhythmic activity

  摘要：

  DOI：

  10.1007/bf02219697
• 作为产物：
  描述：

  亚氨基二苄 在 盐酸 、 硫酸 、 palladium on activated charcoal 、 水 、 氢气 、 硝酸 、 sodium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 6.5h， 生成 3-Carbethoxyamino-10,11-dihydro-5H-dibenzazepin
  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

• Synthesis and antiarrhythmic activity of 3-alkoxycarbonylamino-s-acylaminostilbenes
  作者：A. P. Skoldinov、N. V. Kaverina、A. N. Gritsenko、V. V. Lyskovtsev、H. Wunderlich、A. Stark、L. Zenker、D. Loman、H. Poppe、R. Barch

  DOI：10.1007/bf02219696

  日期：1996.3

  individual compounds, because partial splitting of HBr took place already during the bromination reaction. In order to complete the process of dehydrobromination, the reaction mixture was treated with triethylamine with the formation of 5-chloroacetyl-5Hdibenz[b,f]azepines (Vila, b). An alternative, more general pathway to the synthesis of 5-chloroacylstilbenes VII is that involving the reaction between llb

  许多活性抗抑郁药，例如咪嗪和氯米帕明，属于 5-氨基烷基亚氨基二苄类。同时，一些相应的亚氨基二苄基的 5 氨基酰基衍生物不表现出精神作用，但产生心脏作用[I]。在寻找具有抗心律失常特性且不产生中枢兴奋或镇静作用的新化合物的过程中，我们合成并表征了一组结构相关的亚氨基芪。该系列化合物中先前已知的是抗惊厥药物卡巴西平（5-氨基甲酰衍生物 [2]）和胸腺舒缩药物奥匹莫（5-[3-(N,13-羟乙基哌嗪基)丙基]衍生物 [3]）。从相应的 3-烷氧基羰基氨基-10 开始合成在 C(3) 处含有氨基甲酸酯基团的目标亚氨基二烯 Iah，1 l-二氢-5H-二苯并[b,f]氮杂 (lla, b) [4]。它们与氯乙酰氯反应形成 5-氯乙酰衍生物 (IIIa, c)，然后在四氯化碳介质中在 N-溴代琥珀酰亚胺存在下，在石英灯的光照射下进行选择性溴化。IIIa 和 IIIc 的溴化物不是作为单独的化合物获得的，因为在溴化反应过程中已经发生了
• 3-carbalkoxyamino-5-(alpha-aminopropionyl)-5H-dibenz[b,f]azepines and
  申请人：Arzneimittelwerk Dresden GmbH

  公开号：US05192760A1

  公开（公告）日：1993-03-09

  New 3-carbalkoxyamino-5-(alpha-aminopropionyl)-5H-dibenz[b,f]azepines of formula I and their pharmaceutically acceptable salts were found to be suitable actives for the treatment of cardiac arrhythmia. Previously unknown 3-carbalkoxyamino-5-(alpha-halogenpropionyl)-5H-dibenz[b,f]azepines are obtained from 3-carbalkoxyamino-5H-dibenz[b,f]azepines by reaction with alpha-halogenpropionyl halides. Through their reaction with ammonia, primary amines or secondary amines, the new 3-carbalkoxyamino-5-(alpha-aminopropionyl)-5H-dibenz[b,f]azepines are obtained, which can be optionally converted into their pharmaceutically acceptable acid addition salts.

  公式I的新型3-羧酸酯氨基-5-(α-氨基丙酰基)-5H-二苯[b,f]氮平及其药学上可接受的盐被发现适用于治疗心律失常。通过与α-卤代丙酰卤反应，从3-羧酸酯氨基-5H-二苯[b,f]氮平中获得以前未知的3-羧酸酯氨基-5-(α-卤代丙酰基)-5H-二苯[b,f]氮平。通过与氨、一级胺或二级胺反应，获得新的3-羧酸酯氨基-5-(α-氨基丙酰基)-5H-二苯[b,f]氮平，可选择性地转化为其药学上可接受的酸加成盐。
• 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：——
• Synthesis of a new antiarrhythmic agent — Bonnecor
  作者：A. P. Skoldinov、A. N. Gritsenko、H. Wunderlich、A. Stark、E. Carstens、D. Loman

  DOI：10.1007/bf00766590

  日期：1990.12