1-(3,4-difluorobenzoyl)piperazine

• 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: 1-(3,4-difluorobenzoyl)piperazine
• 英文别名: (3,4-difluorophenyl)-piperazin-1-ylmethanone
• 化学式: C₁₁H₁₂F₂N₂O
• mdl: MFCD07392816
• 分子量: 226.226
• InChiKey: ADUNZIXVJYFOSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3,4-difluorobenzoyl)piperazine 、 4-羧基苯硼酸 在 PyBop 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成
  参考文献：
  名称：

  Expanding the structural diversity of Bcr-Abl inhibitors: Dibenzoylpiperazin incorporated with 1H-indazol-3-amine

  摘要：

  A series of N,N'-dibenzoylpiperazine derivatives incorporated with 1H-indazol-3-amine have been designed, synthesized and evaluated as novel Bcr-Abl inhibitors. Several title compounds exhibited potent inhibitory activity against Bcr-Abl wild type as well as T315I mutant. Two compounds, ha and 12c, strongly suppressed the activity of native and mutant Bcr-Abl. In particular, ha exhibited comparable potency with that of Imatinib. It potently inhibited both Bcr-Abl(WT) and Bcr-AbI(T3151) with IC50 values of 0.014 mu M and 0.45 mu M, respectively. Furthermore, compound ha also inhibited the proliferation of K562 leukemia cancer cells. Therefore, it could serve as promising lead compound for further optimization of Bcr-Abl(WT) and Bcr-Abl(T3151) inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.034
• 作为产物：
  描述：

  3,4-二氟苯甲酸 在 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 1-(3,4-difluorobenzoyl)piperazine
  参考文献：
  名称：

  Discovery of novel Bcr-Abl inhibitors with diacylated piperazine as the flexible linker

  摘要：

  设计、合成并评估了含有灵活的二酰基哌嗪连接剂的四十种化合物，作为新型的Bcr-Abl抑制剂。

  DOI：

  10.1039/c5ob00430f

文献信息

• 一种N,6二苯基嘧啶-4-胺类Bcr-Abl抑制剂 及其制备方法和应用
  申请人：西安交通大学

  公开号：CN104262263B

  公开（公告）日：2017-01-11

  本发明公开了一种N,6二苯基嘧啶‑4‑胺类Bcr‑Abl抑制剂及其制备方法和应用，该抑制剂的结构式为其中R为单取代基或双取代基，取代基为烷基或卤素；R1为单取代基或双取代基，取代基为烷基或卤素。该系列抑制剂体外对ABL1激酶有一定的抑制作用，且能够抑制肿瘤细胞的增殖，可用于抗肿瘤药物的制备，尤其是CML(慢性粒细胞性白血病)药物。本发明提供的N,6二苯基嘧啶‑4‑胺类Bcr‑Abl抑制剂的制备方法，具有原料易得，反应条件温和，反应过程操作简单，所用试剂便宜的优点。
• Expanding the structural diversity of Bcr-Abl inhibitors: Hybrid molecules based on GNF-2 and Imatinib
  作者：Xiaoyan Pan、Jinyun Dong、Ruili Shao、Ping Su、Yaling Shi、Jinfeng Wang、Langchong He

  DOI：10.1016/j.bmcl.2015.08.013

  日期：2015.10

  In order to expand the structural diversity of Bcr-Abl inhibitors, twenty hybrids (series E and P) have been synthesized and characterized based on Imatinib and GNF-2. Their biological activities were evaluated in vitro against human leukemia cells. Most compounds exhibited potent antiproliferative activity against K562 cells, especially for compounds E4, E5 and E7. Furthermore, these new hybrids were also screened for Abl kinase inhibitory activity, and some of them inhibited Abl kinase with low micromolar IC50 values. In particular, compound P3 displayed the most potent activity with IC50 value of 0.017 mu M comparable with that of Imatinib. Molecular docking studies indicated that these novel hybrids fitted well with the active site of Bcr-Abl. These results suggested the great potential of these compounds as novel Bcr-Abl inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.
• Discovery of novel Bcr-Abl inhibitors with diacylated piperazine as the flexible linker
  作者：Xiaoyan Pan、Jinyun Dong、Yaling Shi、Ruili Shao、Fen Wei、Jinfeng Wang、Jie Zhang

  DOI：10.1039/c5ob00430f

  日期：——

  Forty-two compounds with flexible diacylated piperazine linkers were designed, synthesized and evaluated as novel Bcr-Abl inhibitors.

  设计、合成并评估了含有灵活的二酰基哌嗪连接剂的四十种化合物，作为新型的Bcr-Abl抑制剂。
• Expanding the structural diversity of Bcr-Abl inhibitors: Dibenzoylpiperazin incorporated with 1H-indazol-3-amine
  作者：Yuanyuan Shan、Jinyun Dong、Xiaoyan Pan、Lin Zhang、Jie Zhang、Yalin Dong、Maoyi Wang

  DOI：10.1016/j.ejmech.2015.09.034

  日期：2015.11

  A series of N,N'-dibenzoylpiperazine derivatives incorporated with 1H-indazol-3-amine have been designed, synthesized and evaluated as novel Bcr-Abl inhibitors. Several title compounds exhibited potent inhibitory activity against Bcr-Abl wild type as well as T315I mutant. Two compounds, ha and 12c, strongly suppressed the activity of native and mutant Bcr-Abl. In particular, ha exhibited comparable potency with that of Imatinib. It potently inhibited both Bcr-Abl(WT) and Bcr-AbI(T3151) with IC50 values of 0.014 mu M and 0.45 mu M, respectively. Furthermore, compound ha also inhibited the proliferation of K562 leukemia cancer cells. Therefore, it could serve as promising lead compound for further optimization of Bcr-Abl(WT) and Bcr-Abl(T3151) inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.