1-(tert-butyl) 4-(4-fluorophenyl)piperazine-1,4-dicarboxylate | 1372793-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(tert-butyl) 4-(4-fluorophenyl)piperazine-1,4-dicarboxylate
• 英文别名: 4-O-tert-butyl 1-O-(4-fluorophenyl) piperazine-1,4-dicarboxylate
• CAS: 1372793-31-1
• 化学式: C₁₆H₂₁FN₂O₄
• 分子量: 324.352
• InChiKey: PITFBMBVLITKSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  23.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  59.08
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-(tert-butyl) 4-(4-fluorophenyl)piperazine-1,4-dicarboxylate 在 盐酸 、 水 、 potassium carbonate 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 、 丁酮 为溶剂， 生成 4-(2-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-2-oxo-ethyl)-piperazine-1-carboxylic acid 4-fluoro-phenyl ester
  参考文献：
  名称：

  Substituted phenoxypropyl-(R)-2-methylpyrrolidine aminomethyl ketones as histamine-3 receptor inverse agonists

  摘要：

  Optimization of a series of aminomethyl ketone diamine H3R antagonists to reduce the brain exposure by lowering the pKa, led to molecules with improved pharmacokinetic properties. Compounds 9, 19, and 25 had high affinity for human H3R and demonstrated in vivo H3R functional activity in the rat dipsogenia model. Compound 9 displayed modest wake-promoting activity in the rat EEG/EMG model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.081
• 作为产物：
  描述：

  4-氟苯酚 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-(tert-butyl) 4-(4-fluorophenyl)piperazine-1,4-dicarboxylate
  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