3-(5,6-二氢苯并[b][1]苯并氮杂卓-11-基)丙-1-胺 | 2095-95-6

• 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: 3-(5,6-二氢苯并[b][1]苯并氮杂卓-11-基)丙-1-胺
• 英文名称: didesmethylimipramine
• 英文别名: 3-(10,11-dihydrodibenzazepin-5-yl)propylamine；3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine；N,N-didesmethylimipramine；N-desmethyldesipramine；imipramine；Didesipramine；3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propan-1-amine
• CAS: 2095-95-6
• 化学式: C₁₇H₂₀N₂
• 分子量: 252.359
• InChiKey: XJWJQDZWUYUIEM-UHFFFAOYSA-N

物化性质

• 保留指数：
  2220.9

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-(5,6-二氢苯并[b][1]苯并氮杂卓-11-基)丙-1-胺 以21%的产率得到3-[3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)propylamino]-4-amino-1,2,5-thiadiazole-1-oxide
  参考文献：
  名称：

  Tricyclic derivatives and pharmaceutical use

  摘要：

  这项发明描述了作为组胺H.sub.1-拮抗剂有用的三环衍生物。该发明的一个特定化合物是3-[3-(吡啶并[3,2-b][1,4]-苯并噻嗪-10-基)丙基氨基]-4-(吡啶-4-基甲氨基)-1,2,5-噻二唑-1-氧化物。

  公开号：

  US04668671A1
• 作为产物：
  描述：

  亚氨基二苄 在 sodium tetrahydroborate 、 三氟化硼四氢呋喃络合物 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 3-(5,6-二氢苯并[b][1]苯并氮杂卓-11-基)丙-1-胺
  参考文献：
  名称：

  Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene

  摘要：

  Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, K-i = 20 nM; 5-HT2c, K-i = 43 nM) versus the dopamine D-2 receptor (K-i >10,000 nM), as well as the serotonin and norepinephrine transporters (Ki >10,000 nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00023-3

文献信息

• Compounds having effects on serotonin-related systems
  申请人：Eli Lilly and Company

  公开号：US05576321A1

  公开（公告）日：1996-11-19

  A series of hetero-oxy alkanamines are effective pharmaceuticals for the treatment of conditions related to or affected by the reuptake of serotonin and by the serotonin 1.sub.A receptor. The compounds are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal, and for the treatment of depression and other conditions for which serotonin reuptake inhibitors are used.

  一系列的杂氧烷胺类化合物是治疗与血清素再摄取或血清素1A受体有关或受其影响的疾病的有效药物。这些化合物特别适用于缓解尼古丁和烟草戒断症状，以及治疗抑郁症和其他需要使用血清素再摄取抑制剂的疾病。
• DNA-Encoded Dynamic Chemical Library and Its Applications in Ligand Discovery
  作者：Yu Zhou、Chen Li、Jianzhao Peng、Liangxu Xie、Ling Meng、Qingrong Li、Jianfu Zhang、Xiang David Li、Xin Li、Xuhui Huang、Xiaoyu Li

  DOI：10.1021/jacs.8b09277

  日期：2018.11.21

  cooperatively binding small-molecule pairs from large-scale dynamic libraries. Our approach is based on DNA-mediated dynamic hybridization, DNA-encoding, and a photo-cross-linking-based decoding scheme. To demonstrate the generality and performance of this approach, a 10 000-member DNA-encoded dynamic library has been prepared and selected against six protein targets. Specific binders have been identified

  动态组合库 (DCL) 已成为配体发现的有效工具，并成为生物医学研究中的重要发现方式。然而，DCL 的应用受到文库多样性低和能够处理大型文库的分析方法有限的严重阻碍。在这里，我们报告了一种解决此限制的策略，并且可以从大型动态库中选择协作结合的小分子对。我们的方法基于 DNA 介导的动态杂交、DNA 编码和基于光交联的解码方案。为了证明这种方法的通用性和性能，我们准备了一个 10 000 名成员的 DNA 编码动态库，并针对六个蛋白质目标进行了选择。已经为每个目标确定了特定的结合剂，我们已经验证了所选配体对与重要细胞功能有关的靶标的生物活性，包括蛋白质脱乙酰化和 sumoylation。值得注意的是，已经开发了一系列新颖的选择性 Sirtuin-3 抑制剂。我们的研究绕过了 DCL 中的一个主要障碍，并可能为针对生物靶标的配体发现提供一种广泛适用的方法。
• [EN] HECT E3 LIGASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE LIGASE E3 HECT ET LEURS UTILISATIONS
  申请人：IFOM FONDAZIONE ST FIRC DI ONCOLOGIA MOLECOLARE

  公开号：WO2020245213A1

  公开（公告）日：2020-12-10

  The present invention relates to tricyclic derivatives of formula (I), which are useful as inhibitors of HECT-domain-containing E3 ligases, in particular NEDD4. The present invention also refers to pharmaceutical compositions comprising compounds of formula (I), to their medical use and to their process of preparation.

  本发明涉及公式（I）的三环衍生物，其作为HECT结构域含有E3连接酶的抑制剂，特别是NEDD4。本发明还涉及包含公式（I）化合物的药物组合物，它们的医疗用途以及它们的制备方法。
• Sequential Metabolism of Secondary Alkyl Amines to Metabolic-Intermediate Complexes: Opposing Roles for the Secondary Hydroxylamine and Primary Amine Metabolites of Desipramine, (<i>S</i>)-Fluoxetine, and <i>N-</i>Desmethyldiltiazem
  作者：Kelsey L. Hanson、Brooke M. VandenBrink、Kantipudi N. Babu、Kyle E. Allen、Wendel L. Nelson、Kent L. Kunze

  DOI：10.1124/dmd.110.032391

  日期：2010.6

  Three secondary amines desipramine (DES), ( S )-fluoxetine [( S )-FLX], and N -desmethyldiltiazem (MA) undergo N -hydroxylation to the corresponding secondary hydroxylamines [ N -hydroxydesipramine, ( S )- N -hydroxyfluoxetine, and N -hydroxy- N -desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N -desmethyldesipramine, ( S )-norfluoxetine, and N,N -didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine ≫ primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N -dealkylation to N -hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [( S )-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N -methyl-d3-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N -demethylation to N -hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N -hydroxylation rather than N -dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation.

  三种仲胺去甲丙咪嗪（DES）、（S）-氟西汀[（S）-FLX]和N-去甲基地尔硫卓（MA）分别经细胞色素P450 2C11、2C19和3A4催化进行N-羟基化反应，生成相应的仲羟基胺[N-羟基去甲丙咪嗪、（S）-N-羟基氟西汀和N-羟基-N-去甲基地尔硫卓]。同时，也观察到了预期的伯胺产物：N-去甲基去甲丙咪嗪、（S）-去甲氟西汀和N,N-二去甲基地尔硫卓。研究了这些底物和代谢物形成代谢中间体（MI）复合物的过程。在每种情况下，MI复合物积累的初始速率遵循仲羟基胺 > 仲胺 ≫ 伯胺的顺序，表明伯胺代谢物不参与这些仲胺形成MI复合物的过程。此外，在仲胺孵育中积累的伯胺代谢物抑制MI复合物的形成。质量平衡研究表明，N-脱烷基化与N-羟基化的产物比例估计为2.9（DES-CYP2C11）、3.6[（S）-FLX-CYP2C19]和0.8（MA-CYP3A4），表明仲羟基胺是P450介导的仲烷基胺代谢的重要代谢物。与N-甲基-d3-去甲丙咪嗪和CYP2C11的平行研究表明，存在从N-脱甲基化到N-羟基化的显著同位素敏感性转换。这些发现表明，这些仲胺形成MI复合物的主要途径来自N-羟基化而非N-脱烷基化，并且伯胺是MI复合物形成的显著竞争性抑制剂。
• TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
  申请人：Ohlmeyer Michael

  公开号：US20140213578A1

  公开（公告）日：2014-07-31

  Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following phenothiazine, dibenzoazepine and annulene and similar genera:

  本文披露了三环化学调节剂对FOXO转录因子蛋白的调节作用。这些化合物可用于治疗癌症、年龄相关蛋白质毒性、压力引起的抑郁症、炎症和痤疮。这些化合物属于以下苯硫噻嗪、二苯并氮杂环和环戊烯类似物系列：