1-(2,6-二氯苄基)哌嗪 | 102292-50-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(2,6-二氯苄基)哌嗪
• 中文别名: 1-(2,6-二氯苯)哌嗪
• 英文名称: 1-(2,6-dichlorobenzyl)piperazine
• 英文别名: 1-[(2,6-dichlorophenyl)methyl]piperazine
• CAS: 102292-50-2
• 化学式: C₁₁H₁₄Cl₂N₂
• mdl: MFCD02736281
• 分子量: 245.152
• InChiKey: WQTPGHSKQDVCQQ-UHFFFAOYSA-N

物化性质

• 熔点：
  54-62 °C
• 沸点：
  332.4±37.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)
• 闪点：
  >230 °F

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36/37/38
• 海关编码：
  2933599090
• WGK Germany：
  3
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

反应信息

• 作为反应物：
  描述：

  1-(2,6-二氯苄基)哌嗪 在 potassium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 (S)-2-((1-(benzylsulfonyl)pyrrolidin-3-yl)amino)-1-(4-(2,6-dichlorobenzyl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors

  摘要：

  Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition. (c) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.020
• 作为产物：
  描述：

  2,6-二氯苄基溴 在 盐酸 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 14.17h， 生成 1-(2,6-二氯苄基)哌嗪
  参考文献：
  名称：

  [EN] MULTIVALENT RAS BINDING COMPOUNDS
  [FR] COMPOSÉS DE LIAISON RAS MULTIVALENTS

  摘要：

  本文描述了调节Ras信号传导的化合物，制备这种化合物的方法，包含这种化合物的药物组合物和药物，以及使用这种化合物治疗与改变的Ras信号传导相关的疾病、疾病或紊乱的方法。此外，本文还描述了化合物、制备这种化合物的方法、包含这种化合物的药物组合物和药物，并且使用这种化合物治疗细胞增殖紊乱，包括癌症的方法。

  公开号：

  WO2017096045A1

文献信息

• Synthesis and biological evaluation as AChE inhibitors of new indanones and thiaindanones related to donepezil
  作者：Ziad Omran、Thomas Cailly、Elodie Lescot、Jana Sopkova-de Oliveira Santos、Jean-Hugues Agondanou、Vincent Lisowski、Frédéric Fabis、Anne-Marie Godard、Silvia Stiebing、Guillaume Le Flem、Michel Boulouard、François Dauphin、Patrick Dallemagne、Sylvain Rault

  DOI：10.1016/j.ejmech.2005.07.009

  日期：2005.12

  Sixty-four new indanones and thiaindanones related to donepezil were synthesized and evaluated in vitro as potential AChE inhibitors. Among them, 11 derivatives were found to inhibit the enzyme in the submicromolar range; the best compound revealed its inhibitory activity with an IC50 in the same range (0.06 microM) than the reference compound, donepezil (IC50=0.02 microM).

  合成了与多奈哌齐有关的六十四种新的茚满酮和硫丹酮，并在体外评估了其作为潜在的AChE抑制剂。其中，发现了11种衍生物在亚微摩尔范围内抑制该酶。最好的化合物显示出其抑制活性，其IC50与参考化合物多奈哌齐（IC50 = 0.02 microM）处于相同范围（0.06 microM）。
• [EN] QUINOXALINE DERIVATIVES AS GPR6 MODULATORS<br/>[FR] DÉRIVÉS DE QUINOXALINE EN TANT QUE MODULATEURS DU GPR6
  申请人：ENVOY THERAPEUTICS INC

  公开号：WO2014028479A1

  公开（公告）日：2014-02-20

  The present invention provides compounds of Formula (I) that are GPR6 modulators and are therefore useful for the treatment of diseases treatable by modulation of GPR6, in particular treating Parkinson disease, levodopa induced dyskinesias, Huntington's disease, other dyskinesias, akinesias, and motor disorders involving dysfunction of the striatum, schizophrenia and drug addiction. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本发明提供了式(I)化合物，该化合物是GPR6调节剂，因此可用于治疗可通过调节GPR6来治疗的疾病，特别是治疗帕金森病、左旋多巴诱导的舞蹈病、亨廷顿病、其他舞蹈病、运动不能、涉及纹状体功能障碍的运动障碍、精神分裂症和药物成瘾。还提供了含有此类化合物的药物组合物以及制备此类化合物的过程。
• INHIBITORS OF STEAROYL-COA DESATURASE
  申请人：Gillespie Paul

  公开号：US20090149466A1

  公开（公告）日：2009-06-11

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity.

  提供以下式(I)化合物： 以及药用可接受的盐，其中取代基如说明书中所披露。这些化合物以及包含它们的药物组合物可用于治疗诸如肥胖等疾病。
• [EN] SMALL MOLECULE RAS LIGANDS<br/>[FR] LIGANDS RAS DE PETITES MOLÉCULES
  申请人：UNIV COLUMBIA

  公开号：WO2016176338A1

  公开（公告）日：2016-11-03

  The present invention provides compounds that selectively bind a RAS protein at three or more sites, which compounds selectively bind to a first site on the RAS protein that includes at least one amino acid near L56. Pharmaceutical compositions including a pharmaceutically acceptable carrier and a compound of the present invention are also provided. Methods and kits for treating or ameliorating the effects of a disease associated with altered RAS signaling in a subject are also provided. Methods, kits and compositions which include such compounds also are provided.

  本发明提供了一种选择性地在RAS蛋白的三个或更多位点结合的化合物，这些化合物选择性地结合到RAS蛋白上的第一个位点，该位点包括至少一个接近L56的氨基酸。还提供了包括药用可接受载体和本发明化合物的药物组合物。还提供了用于治疗或改善与受改变的RAS信号传导相关的疾病的方法和试剂盒。还提供了包括这些化合物的方法、试剂盒和组合物。
• Discovery and biological evaluation of phthalazines as novel non-kinase TGFβ pathway inhibitors
  作者：Anupreet Kharbanda、Lingtian Zhang、Debasmita Saha、Phuc Tran、Ke Xu、Ming O. Li、Yuet-Kin Leung、Brendan Frett、Hong-yu Li

  DOI：10.1016/j.ejmech.2021.113660

  日期：2021.11

  is one of vital clinical interest. Despite various attempts, there is still no FDA-approved therapy to inhibit the TGFβ pathway. Major mainstream approaches involve impairment of the TGFβ pathway via inhibition of the TGFβRI kinase. With the purpose to identify non-receptor kinase-based inhibitors to impair TGFβ signaling, an in-house chemical library was enriched, through a computational study, to

  TGFβ对于上皮和神经组织的稳态、伤口修复和调节免疫反应至关重要。其失调与大量疾病有关，其中改变肿瘤微环境是重要的临床意义之一。尽管进行了各种尝试，但仍然没有 FDA 批准的抑制 TGFβ 途径的疗法。主要的主流方法包括通过以下方式损伤 TGFβ通路抑制TGFβRI激酶。为了识别基于非受体激酶的抑制剂以损害 TGFβ 信号传导，通过计算研究丰富了内部化学库，以消除 TGFβRI 激酶活性。针对在 TGFβ-Smad 依赖性转录控制下用萤火虫荧光素酶基因改造的细胞系筛选选定的化合物。结果表明具有酞嗪核心的分子对 TGFβ-Smad 信号传导具有中等效力。合成了一系列酞嗪化合物并评估其效力。最有希望的化合物 ( 10p ) 的 IC 50为 0.11 ± 0.02 μM，经证实在高达 12 μM 时无细胞毒性，选择性指数约为 112 倍。同时，10p证实使用蛋白质印迹可减少 Smad 磷酸化，而不显示对