1-(2-溴苄基)-哌嗪 | 298705-59-6

• 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-溴苄基)-哌嗪
• 中文别名: 1-(2-溴苯基)哌嗪
• 英文名称: 1-(2-bromo-benzyl)-piperazine
• 英文别名: 1-(2-bromobenzyl)piperazine；1-[(2-bromophenyl)methyl]piperazine
• CAS: 298705-59-6
• 化学式: C₁₁H₁₅BrN₂
• mdl: MFCD02040754
• 分子量: 255.157
• InChiKey: XVHSZKUVDNZYDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 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

• 危险品标志：
  Xi
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  丁二酰氯 、 1-(2-溴苄基)-哌嗪 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 1,4-bis-[4-(2-bromo-benzyl)-piperazin-1-yl]butane-1,4-dione
  参考文献：
  名称：

  Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors

  摘要：

  Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.

  DOI：

  10.1016/s0014-827x(03)00150-2
• 作为产物：
  描述：

  叔-丁基 4-(2-溴苯甲基)哌嗪-1-羧酸酯 在 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 3.0h， 以77%的产率得到1-(2-溴苄基)-哌嗪
  参考文献：
  名称：

  Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors

  摘要：

  Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.

  DOI：

  10.1016/s0014-827x(03)00150-2

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）。
• Novel N-acylated heterocycles
  申请人：Recordati S.A.

  公开号：US20030162777A1

  公开（公告）日：2003-08-28

  Described are compositions comprising a muscarinic receptor antagonist and an N-acylated heterocycle derivative having affinity for serotonergic receptors, and enantiomers, diastereoisomers, N-oxides, polymorphs, solvates and pharmaceutically acceptable salts thereof. The combination of a muscarinic receptor antagonist and an N-acylated heterocycle, or an enantiomer, diastereoisomer, N-oxide, polymorph, solvate or pharmaceutically acceptable salt thereof, is useful in the treatment of patients with neuromuscular dysfunction of the lower urinary tract and diseases related to 5-HT 1A receptors.

  描述了包含一种肌氨酸受体拮抗剂和一种对5-HT 1A 受体具有亲和力的N-酰化杂环衍生物的组合物，以及它们的对映体、二对映体、N-氧化物、多型体、溶剂合物和药用可接受盐。肌氨酸受体拮抗剂和N-酰化杂环，或其对映体、二对映体、N-氧化物、多型体、溶剂合物或药用可接受盐的组合，在治疗患有下尿路神经肌肉功能障碍和与5-HT 1A 受体相关疾病的患者中是有用的。
• 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。
• Synthesis and Preliminary Pharmacological Evaluation of 4´-Arylmethyl Analogues of Clozapine. I. The Effect of Aromatic Substituents
  作者：B. Capuano、I. T. Crosby、E. J. Lloyd、D. A. Taylor

  DOI：10.1071/ch02093

  日期：——

  dopamine D4 and serotonin 5-HT2A antagonist activity with potential for the treatment of schizophrenia, we report a family of compounds based on structural modification of the atypical antipsychotic, clozapine (2). The chemical synthesis, structural characterization and pharmacological evaluation of a series 4�-arylmethyl analogues of clozapine are described. Preliminary receptor binding data are presented

  作为开发具有混合多巴胺 D4 和 5-HT2A 拮抗剂活性且具有治疗精神分裂症潜力的化合物的研究计划的一部分，我们报告了基于非典型抗精神病药物氯氮平 (2) 的结构修饰的化合物家族。描述了一系列 4’-芳甲基氯氮平类似物的化学合成、结构表征和药理学评价。提供了初步的受体结合数据，主要检查取代基对引入的芳甲基的电子和位置影响，其次是芳环的性质。
• 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