1-(2-氯乙基)-4-[(4-氯苯基)(苯基)甲基]哌嗪 | 102163-64-4

• 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-氯乙基)-4-[(4-氯苯基)(苯基)甲基]哌嗪
• 英文名称: 1-(2-chloroethyl)-4-[(4-chlorophenyl)(phenyl)methyl]piperazine
• 英文别名: 1-(2-chloro-ethyl)-4-(4-chloro-benzhydryl)-piperazine；1-(2-Chlor-aethyl)-4-(4-chlor-benzhydryl)-piperazin；1-(2-Chloroethyl)-4-[(4-chlorophenyl)-phenyl-methyl]piperazine；1-(2-chloroethyl)-4-[(4-chlorophenyl)-phenylmethyl]piperazine
• CAS: 102163-64-4
• 化学式: C₁₉H₂₂Cl₂N₂
• 分子量: 349.303
• InChiKey: ZJIVFSMHFMGJMV-UHFFFAOYSA-N

物化性质

• 沸点：
  446.6±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-氯乙基)-4-[(4-氯苯基)(苯基)甲基]哌嗪 在 盐酸 、 potassium carbonate 作用下， 以 水 为溶剂， 反应 6.0h， 生成 1-((4-chlorophenyl)(phenyl)methyl)-4-(2-(piperazin-1-yl)ethyl)piperazine
  参考文献：
  名称：

  Identification, Characterization and Synthesis of Process Related Unknown Impurity in Cetirizine Dihydrochloride

  摘要：

  本文描述了二盐酸西替利嗪中未知杂质的鉴定、分离、结构表征和合成过程。通过梯度 HPLC 和 LC-MS 方法检测到二盐酸西替利嗪中与工艺相关的未知杂质含量在 0.1-0.15% 范围内。根据LC-ESI/MSn研究，推测杂质的化学结构为2-(2-(4-(2-(4-((4-氯苯基)(苯基)甲基)哌嗪-1-基)乙基)哌嗪-1-基)乙氧基)乙酸。通过制备型 HPLC 分离杂质，完整的光谱分析、MS、1D NMR（1H 和 13C）、2D NMR（COSY、HSQC 和 HMBC）证实了杂质的拟议化学结构。

  DOI：

  10.14233/ajchem.2017.20223
• 作为产物：
  描述：

  1-(4-氯二苯甲基)哌嗪 在 氯化亚砜 作用下， 生成 1-(2-氯乙基)-4-[(4-氯苯基)(苯基)甲基]哌嗪
  参考文献：
  名称：

  An assembly of structurally diverse small and simple 5-aminomethylene derivatives of 2,4-thiazolidinedione and studies of their biological activity

  摘要：

  The synthesis of a novel series of substituted 5-(aminomethylene)thiazolidine-2,4-diones was achieved using a wide range of heterocyclic models derived from eight drug-like molecules. The primary aim of this study was to combine medicinally known, biologically active molecules bearing a 2A degrees amine functionality, such as terbinafine, fluoxetine, atomoxetine, cetirizine, risperidone, aripiprazole, ziprasidone, and clopidogrel, with a thiazolidinedione ring via an amino-methylene linker. By targeting this synergistic approach to compounds with skeletal, functional, and stereochemical diversity, we have developed a simple synthetic concept to enrich the thiazolidinedione collection with various biological activities. The biological activities of the newly synthesized 5-(aminomethylene)thiazolidine-2,4-dione derivatives were explored. All compounds were found to have antibacterial activity, with compounds bearing pyridine or piperazine moieties showing good to excellent antibacterial activity. Compounds with piperazine moieties were also found to show good antifungal activity, whereas none of the synthesized compounds showed high cytotoxic activity.

  DOI：

  10.1007/s00044-015-1447-0

文献信息

• Synthesis of Azole-containing Piperazine Derivatives and Evaluation of their Antibacterial, Antifungal and Cytotoxic Activities
  作者：Lin-Ling Gan、Bo Fang、Cheng-He Zhou

  DOI：10.5012/bkcs.2010.31.12.3684

  日期：2010.12.20

  A series of azole-containing piperazine derivatives have been designed and synthesized. The obtained compounds were investigated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that most compounds exhibited moderate to significant antibacterial and antifungal activities in vitro. 1-(4-((4-chlorophenyl) (phenyl)methyl)piperazin-1-yl)-2-(1H-imidazol-1-yl)ethanone and 1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)-2-(2-phenyl-1H-imidazol-1-yl)ethanone gave remarkable and broad-spectrum antimicrobial efficacy against all tested strains with MIC values ranging from 3.1 to $25\;\mu}g/mL$, and exhibited comparable activities to the standard drugs chloramphenicol and fluconazole in clinic. Moreover, 2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-1H-benzo[d]imidazole was found to be the most effective in vitro against the PC-3 cell line, reaching growth inhibition values (36.4, 60.1 and 76.5%) for each tested concentration: $25\;\mu}g/mL$, $50\;\mu}g/mL$ and $100\;\mu}g/mL$ in dose-dependent manner. The results also showed that the azole ring had noticeable effect on their antimicrobial and cytotoxic activities, and imidazole and benzimidazole moiety were much more favourable to biological activity than 1,2,4-triazole.

  设计并合成了一系列含有三唑环的哌嗪衍生物。所得化合物在体外进行了抗菌、抗真菌和细胞毒性活性的研究。初步结果表明，大多数化合物在体外表现出中等到显著的抗菌和抗真菌活性。1-(4-((4-氯苯基)(苯基)甲基)哌嗪-1-基)-2-(1H-咪唑-1-基)乙酮和1-(4-((4-氯苯基)(苯基)甲基)哌嗪-1-基)-2-(2-苯基-1H-咪唑-1-基)乙酮对所有测试菌株显示出显著且广谱的抗微生物效力，MIC值范围为3.1至$25\;\mu}g/mL$，并显示出与临床标准药物氯霉素和氟康唑相当的活性。此外，2-((4-((4-氯苯基)(苯基)甲基)哌嗪-1-基)甲基)-1H-苯并[d]咪唑在体外对PC-3细胞系最为有效，其生长抑制值（分别为36.4%、60.1%和76.5%）按剂量依赖方式对应于$25\;\mu}g/mL$、$50\;\mu}g/mL$和$100\;\mu}g/mL$的测试浓度。结果还显示，三唑环对其抗微生物和细胞毒性活性有明显影响，咪唑和苯并咪唑部分比1,2,4-三唑更有利于生物活性。
• Design, Synthesis and Antifungal Activity of Some New Imidazole and Triazole Derivatives
  作者：Zahra Rezaei、Soghra Khabnadideh、Kamiar Zomorodian、Kyvan Pakshir、Giti Kashi、Narges Sanagoei、Sanaz Gholami

  DOI：10.1002/ardp.201000357

  日期：2011.10

  Triazole and imidazole are incorporated into the structures of many antifungal compounds. In this study a novel series of 1,2,4‐triazole, imidazole, benzoimidazole, and benzotriazole derivatives was designed as inhibitors of cytochrome P450 14α‐demethylase (14DM). These structures were docked into the active site of MT‐CYP51, using Autodock program. Sixteen compounds with the best binding energy were

  三唑和咪唑被结合到许多抗真菌化合物的结构中。在这项研究中，设计了一系列新的 1,2,4-三唑、咪唑、苯并咪唑和苯并三唑衍生物作为细胞色素 P450 14α-脱甲基酶 (14DM) 的抑制剂。使用 Autodock 程序将这些结构对接到 MT-CYP51 的活性位点。合成了具有最佳结合能的 16 种化合物。新化合物的化学结构通过元素和光谱（1H-NMR 和质谱）分析得到证实。研究了所有化合物对白色念珠菌、热带念珠菌、光滑念珠菌、近皮念珠菌、克鲁泽念珠菌、都柏林念珠菌、烟曲霉、黄曲霉、犬小孢子菌、石膏小孢子菌、毛癣菌属植物的抗真菌活性。一些化合物对大多数测试的真菌显示出优异的体外抗真菌活性。化合物 2、9 和 10 对几种对氟康唑和伊曲康唑的耐药真菌具有抗真菌活性。
• Morren et al., Industrie Chimique Belge, 1954, vol. 19, p. 1176,1181
  作者：Morren et al.

  DOI：——

  日期：——
• An assembly of structurally diverse small and simple 5-aminomethylene derivatives of 2,4-thiazolidinedione and studies of their biological activity
  作者：Sandeep Mohanty、Sandeep G. Reddy、B. RamaDevi、Arun Chandra Karmakar

  DOI：10.1007/s00044-015-1447-0

  日期：2015.12

  The synthesis of a novel series of substituted 5-(aminomethylene)thiazolidine-2,4-diones was achieved using a wide range of heterocyclic models derived from eight drug-like molecules. The primary aim of this study was to combine medicinally known, biologically active molecules bearing a 2A degrees amine functionality, such as terbinafine, fluoxetine, atomoxetine, cetirizine, risperidone, aripiprazole, ziprasidone, and clopidogrel, with a thiazolidinedione ring via an amino-methylene linker. By targeting this synergistic approach to compounds with skeletal, functional, and stereochemical diversity, we have developed a simple synthetic concept to enrich the thiazolidinedione collection with various biological activities. The biological activities of the newly synthesized 5-(aminomethylene)thiazolidine-2,4-dione derivatives were explored. All compounds were found to have antibacterial activity, with compounds bearing pyridine or piperazine moieties showing good to excellent antibacterial activity. Compounds with piperazine moieties were also found to show good antifungal activity, whereas none of the synthesized compounds showed high cytotoxic activity.
• Identification, Characterization and Synthesis of Process Related Unknown Impurity in Cetirizine Dihydrochloride
  作者：Jagadeesh Narkedimilli、Ravindra Kumar Yalavarthi、Sandeep Mohanty、Kirti Kumar Jain、Sandeep Reddy Gaddam、Jayashree Anireddy

  DOI：10.14233/ajchem.2017.20223

  日期：——

  Identification, isolation, structural characterization and synthesis of process generated unknown impurity in cetirizine dihydrochloride is described in this work. Process-related unknown impurity was detected in the range of 0.1-0.15 % in cetirizine dihydrochloride by a gradient HPLC and LC-MS methods. Based on LC-ESI/MSn study, the chemical structure of impurity was presumed as 2-(2-(4-(2-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethyl)piperazin-1-yl)ethoxy)acetic acid. The impurity was isolated by preparative HPLC, the complete spectral analysis, MS, 1D NMR (1H and 13C), 2D NMR (COSY, HSQC and HMBC) confirmed the proposed chemical structure of impurity.

  本文描述了二盐酸西替利嗪中未知杂质的鉴定、分离、结构表征和合成过程。通过梯度 HPLC 和 LC-MS 方法检测到二盐酸西替利嗪中与工艺相关的未知杂质含量在 0.1-0.15% 范围内。根据LC-ESI/MSn研究，推测杂质的化学结构为2-(2-(4-(2-(4-((4-氯苯基)(苯基)甲基)哌嗪-1-基)乙基)哌嗪-1-基)乙氧基)乙酸。通过制备型 HPLC 分离杂质，完整的光谱分析、MS、1D NMR（1H 和 13C）、2D NMR（COSY、HSQC 和 HMBC）证实了杂质的拟议化学结构。