[4-(Trifluoromethyl)phenyl] piperazine-1-carboxylate | 1224438-89-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-(Trifluoromethyl)phenyl] piperazine-1-carboxylate
• 英文别名: [4-(trifluoromethyl)phenyl] piperazine-1-carboxylate
• CAS: 1224438-89-4
• 化学式: C₁₂H₁₃F₃N₂O₂
• 分子量: 274.243
• InChiKey: HMBMFFDGSCXSDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.11
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  41.57
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  [4-(Trifluoromethyl)phenyl] piperazine-1-carboxylate 、 (5aS,6R,8aS,9S,11R,11aR)-3,6,9-trimethyloctahydro-3H,11H-3,11-epoxy[1,2]dioxepino[3,4-d]isobenzofuran-9-carboxylic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以50%的产率得到4-(trifluoromethyl)phenyl 4-((5aS,6R,8aS,9S,11R,11aR)-3,6,9-trimethyloctahydro-3H,11H-3,11-epoxy[1,2]dioxepino[3,4-d]isobenzofuran-9-carbonyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Novel artemisinin derivatives with potent anticancer activities and the anti-colorectal cancer effect by the mitochondria-mediated pathway

  摘要：

  Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS technologies. The in vitro cytotoxicity against various cancer cell lines was evaluated. Among the derivatives, compound 12h was found to exhibit not only the best activity against HCT-116 cells (IC₅₀ = 0.12 ± 0.05 μM), but also low toxicity against normal cell line L02 (IC₅₀ = 12.46 ± 0.10 μM). The mechanisms study revealed that compound 12h caused the cell cycle arrest in G1 phase, induced apoptosis in a concentration-dependent manner, significantly reduced mitochondrial membrane potential, increased intracellular ROS and Ca²⁺ levels, up-regulated the expression of Bax, cleaved caspase-9, cleaved caspase-3, and down-regulated the expression of Bcl-2 protein. A series of analyses confirmed that 12h can inhibit HCT-116 cells migration and induce apoptosis by a mechanism of the mitochondria-mediated pathway in the HCT-116 cell line. The present work indicates that compound 12h may merit further investigation as a potential therapeutic agent for colorectal cancer.

  DOI：

  10.1016/j.bioorg.2020.104496
• 作为产物：
  描述：

  对三氟甲基苯酚 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 [4-(Trifluoromethyl)phenyl] piperazine-1-carboxylate
  参考文献：
  名称：

  Novel artemisinin derivatives with potent anticancer activities and the anti-colorectal cancer effect by the mitochondria-mediated pathway

  摘要：

  Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS technologies. The in vitro cytotoxicity against various cancer cell lines was evaluated. Among the derivatives, compound 12h was found to exhibit not only the best activity against HCT-116 cells (IC₅₀ = 0.12 ± 0.05 μM), but also low toxicity against normal cell line L02 (IC₅₀ = 12.46 ± 0.10 μM). The mechanisms study revealed that compound 12h caused the cell cycle arrest in G1 phase, induced apoptosis in a concentration-dependent manner, significantly reduced mitochondrial membrane potential, increased intracellular ROS and Ca²⁺ levels, up-regulated the expression of Bax, cleaved caspase-9, cleaved caspase-3, and down-regulated the expression of Bcl-2 protein. A series of analyses confirmed that 12h can inhibit HCT-116 cells migration and induce apoptosis by a mechanism of the mitochondria-mediated pathway in the HCT-116 cell line. The present work indicates that compound 12h may merit further investigation as a potential therapeutic agent for colorectal cancer.

  DOI：

  10.1016/j.bioorg.2020.104496

文献信息

• Dual Nickel Photocatalysis for <i>O</i>-Aryl Carbamate Synthesis from Carbon Dioxide
  作者：Aleksi Sahari、Jukka Puumi、Jere K. Mannisto、Timo Repo

  DOI：10.1021/acs.joc.3c00023

  日期：2023.3.17

  photocatalyst-mediated reduction of Ni(II) to Ni(I) and subsequent oxidative addition of the aryl halide. The physical properties of the photocatalyst were critical for promoting formation of O-aryl carbamates over various byproducts. Nine new phthalonitrile photocatalysts were synthesized, which exhibited properties that were vital to achieve high selectivity and activity.

  我们报告了双镍光催化在从芳基碘化物或溴化物、胺和二氧化碳合成O-芳基氨基甲酸酯中的应用。反应在可见光下、环境二氧化碳压力下进行，并且没有化学计量的活化剂。机理分析与 Ni(I-III) 循环一致，其中活性物质由光催化剂产生。限速步骤是光催化剂介导的 Ni(II) 还原为 Ni(I) 和随后芳基卤化物的氧化加成。光催化剂的物理性质对于促进O的形成至关重要- 各种副产品上的芳基氨基甲酸酯。合成了九种新的苯二甲腈光催化剂，它们表现出对于实现高选择性和活性至关重要的特性。
• Synthesis and biological evaluation of piperazinyl carbamates and ureas as fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channel dual ligands
  作者：Enrico Morera、Luciano De Petrocellis、Ludovica Morera、Aniello Schiano Moriello、Alessia Ligresti、Marianna Nalli、David F. Woodward、Vincenzo Di Marzo、Giorgio Ortar

  DOI：10.1016/j.bmcl.2009.09.033

  日期：2009.12

  The evaluation of a series of piperazinyl carbamates and ureas, designed on the basis of previously reported TRPV1 antagonists and FAAH inhibitors, led to the identification of some 'dual-action' compounds targeting both FAAH and TRPV1 or TRPA1 receptors. (C) 2009 Elsevier Ltd. All rights reserved.