desipramine | 2095-88-7

• 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: desipramine
• 英文别名: 2-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-methylethanamine；2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylethan-1-amine；5-(2-Methylaminoethyl)-iminodibenzyl
• CAS: 2095-88-7
• 化学式: C₁₇H₂₀N₂
• 分子量: 252.359
• InChiKey: HMXWJSVLYABURQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 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：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  desipramine 、 2-(4-甲氧苯基)-氯乙烷 在 正丁基锂 、 三异丁基铝 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 1.0h， 以30%的产率得到N-[2-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)ethyl]-2-(4-methoxyphenyl)-N-methylethanamine
  参考文献：
  名称：

  NB 06: From a simple lysosomotropic aSMase inhibitor to tools for elucidating the role of lysosomes in signaling apoptosis and LPS-induced inflammation

  摘要：

  Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C-6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli induced increase of C-16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis. Compounds like NB 06 thus offer highly interesting fields of application besides prevention of apoptosis of macrophages in atherosclerotic plaques in vessel walls. Most importantly, they can be used for blocking pH dependent lysosomal processes and enzymes in general as well as for analyzing lysosomal dependent cellular signaling. Modulation of gene expression of several prominent inflammatory messengers IL1B, IL6, IL23A, CCL4 and CCL20 further indicate potentially beneficial effects in the field of (systemic) infections involving bacterial endotoxins like LPS or infections with influenza A virus. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.09.021
• 作为产物：
  描述：

  亚氨基二苄 在 正丁基锂 、 1,8-双二甲氨基萘 作用下， 以 正己烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 2.5h， 生成 desipramine
  参考文献：
  名称：

  NB 06: From a simple lysosomotropic aSMase inhibitor to tools for elucidating the role of lysosomes in signaling apoptosis and LPS-induced inflammation

  摘要：

  Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C-6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli induced increase of C-16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis. Compounds like NB 06 thus offer highly interesting fields of application besides prevention of apoptosis of macrophages in atherosclerotic plaques in vessel walls. Most importantly, they can be used for blocking pH dependent lysosomal processes and enzymes in general as well as for analyzing lysosomal dependent cellular signaling. Modulation of gene expression of several prominent inflammatory messengers IL1B, IL6, IL23A, CCL4 and CCL20 further indicate potentially beneficial effects in the field of (systemic) infections involving bacterial endotoxins like LPS or infections with influenza A virus. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.09.021

文献信息

• Direct electrophilic <i>N</i>-trifluoromethylthiolation of amines with trifluoromethanesulfenamide
  作者：Sébastien Alazet、Kevin Ollivier、Thierry Billard

  DOI：10.3762/bjoc.9.270

  日期：——

  The CF₃SN moiety is a substituent with interesting properties. However, there is no easy synthetic access to molecules bearing this group. The trifluoromethanesulfenamide is a new reagent for the electrophilic trifluoromethylthiolation which reacts easily with amines to obtain trifluoromethylsulfanylamines with good yields.

  CF₃SN基团是一个具有有趣性质的取代基。然而，目前还没有简便的合成方法来获得带有这个基团的分子。三氟甲硫酰氟化铵是一种新的试剂，用于进行亲电三氟甲硫基化反应，它可以容易地与胺类化合物反应，以良好的产率获得三氟甲硫基胺。

• A Focused Library of Psychotropic Analogues with Neuroprotective and Neuroregenerative Potential
  作者：Elisa Uliassi、Luis Emiliano Peña-Altamira、Aixa V. Morales、Francesca Massenzio、Sabrina Petralla、Michele Rossi、Marinella Roberti、Loreto Martinez Gonzalez、Ana Martinez、Barbara Monti、Maria Laura Bolognesi

  DOI：10.1021/acschemneuro.8b00242

  日期：2019.1.16

  Overcoming the lack of effective treatments and the continuous clinical trial failures in neurodegenerative drug discovery might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting simultaneously neuroprotection and neuroregeneration. In the studies reported herein, we sought to identify small molecules that might exert neuroprotective and neuroregenerative potential as tools against neurodegenerative diseases. In doing so, we started from the reported neuroprotective/neuroregenerative mechanisms of psychotropic drugs featuring a tricyclic alkylamine scaffold. Thus, we designed a focused-chemical library of 36 entries aimed at exploring the structural requirements for efficient neuroprotective/neuroregenerative cellular activity, without the manifestation of toxicity. To this aim, we developed a synthetic protocol, which overcame the limited applicability of previously reported procedures. Next, we evaluated the synthesized compounds through a phenotypic screening pipeline, based on primary neuronal systems. Phenothiazine 2Bc showed improved neuroregenerative and neuroprotective properties with respect to reference drug desipramine (2Aa). Importantly, we have also shown that 2Bc outperformed currently available drugs in cell models of Alzheimer's and Parkinson's diseases and attenuates microglial activation by reducing iNOS expression.