2-chloro-1-[4-(4-fluorobenzyl)piperazin-1-yl]ethanone

• 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: 2-chloro-1-[4-(4-fluorobenzyl)piperazin-1-yl]ethanone
• 英文别名: 2-chloro-1-(4-(4-fluorobenzyl)piperazin-1-yl)ethan-1-one；2-Chloro-1-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]ethanone
• 化学式: C₁₃H₁₆ClFN₂O
• 分子量: 270.734
• InChiKey: YGNLXFUYBNWTOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-1-[4-(4-fluorobenzyl)piperazin-1-yl]ethanone 、 5-氯-8-羟基喹啉 生成 1-((5-chloroquinolin-8-yloxy)methyl)carbonyl-4-(4-fluorobenzyl)piperazine
  参考文献：
  名称：

  Piperazine derivatives and their use as anti-inflammatory agents

  摘要：

  公开号：

  EP1254899B1
• 作为产物：
  描述：

  4-氟氯苄 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 9.5h， 生成 2-chloro-1-[4-(4-fluorobenzyl)piperazin-1-yl]ethanone
  参考文献：
  名称：

  设计，合成和评价吡咯嗪衍生物作为二环酪氨酸（cYY）模拟物的结核分枝杆菌

  摘要：

  三个系列唑哌嗪衍生物的模拟dicyclotyrosine（CYY），必需的天然底物的结核分枝杆菌的细胞色素P450 CYP121A1，制备并评价针对结合亲和力和抑制活性（MIC）的结核分枝杆菌。系列A替代了一个酚基团CYY的与C3-咪唑部分，系列B包括在系列A咪唑之前的烃链上的酮基，而C系列探索用CH替换CYY的哌啶酮环的酮基2 -咪唑或CH 2-三唑部分，以增强与CYP121A1血红素的结合相互作用。除B 10a系列外，该系列对CYP121A1显示中等至弱II型结合亲和力，其中显示了混合的I型绑定。在这三个系列中，系列C咪唑衍生物显示出对结核分枝杆菌的最佳抑制作用，尽管抑制作用适中（17d MIC = 12.5μg/ mL，17a 50μg/ mL）。确定了与系列A化合物6a和6b结合的CYP121A1的晶体结构，这些化合物显示，咪唑基团位于血红素铁的正上方，并且两个化合物的血红素铁和咪唑氮之间的键合距离为2

  DOI：

  10.1016/j.bmc.2017.11.030

文献信息

• Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors
  作者：Cunlong Zhang、Chunyan Tan、Xuyu Zu、Xin Zhai、Feng Liu、Bizhu Chu、Xiaohua Ma、Yuzong Chen、Ping Gong、Yuyang Jiang

  DOI：10.1016/j.ejmech.2011.01.020

  日期：2011.4

  Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition. (c) 2011 Elsevier Masson SAS. All rights reserved.
• Indole-nitroimidazole conjugates as efficient manipulators to decrease the genes expression of methicillin-resistant Staphylococcus aureus
  作者：Zhen-Zhen Li、Vijai Kumar Reddy Tangadanchu、Narsaiah Battini、Rammohan R. Yadav Bheemanaboina、Zhong-Lin Zang、Shao-Lin Zhang、Cheng-He Zhou

  DOI：10.1016/j.ejmech.2019.06.093

  日期：2019.10

  The biological resistance of methicillin-resistant staphylococcus aureus (MRSA) has pushed synthetic antibiotics to the forefront. To combat the resistance of MRSA, our new effort directed towards the development of novel structural candidates of enone-bridged indole nitroimidazole scaffolds, and wished to shed some light on the combination of some single pharmacophore with different biological activities. Bioassay revealed that the active compound 4b gave a satisfactory inhibition on MRSA (MIC = 1 mu g/mL) and could effectively prevent the development of bacterial resistance. Mechanism exploration indicated that molecule 4b could not only intercalate into MRSA deoxyribonucleic acid (DNA), but also permeate MRSA membrane and bind with penicillin-binding protein 2a (PBP2a), then decreased the expression of three relevant genes in MRSA. Furthermore, it was able to be stored and carried by human serum albumin (HSA), and the participation of metal ions in 4b-HSA system was helpful to improve the supramolecular transport behavior. Hybrid 4b also exhibited low cytotoxicity towards normal lung epithelial cell line BEAS-2B. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Piperazine derivatives and their use as anti-inflammatory agents
  申请人：Schering Aktiengesellschaft

  公开号：EP1254899B1

  公开（公告）日：2005-05-25
• Design, synthesis and evaluation against Mycobacterium tuberculosis of azole piperazine derivatives as dicyclotyrosine (cYY) mimics
  作者：Hend A.A. Abd El-wahab、Mauro Accietto、Leonardo B. Marino、Kirsty J. McLean、Colin W. Levy、Hamdy M. Abdel-Rahman、Mahmoud A. El-Gendy、Andrew W. Munro、Ahmed S. Aboraia、Claire Simons

  DOI：10.1016/j.bmc.2017.11.030

  日期：2018.1

  interaction with the heme of CYP121A1. The series displayed moderate to weak type II binding affinity for CYP121A1, with the exception of series B 10a, which displayed mixed type I binding. Of the three series, series C imidazole derivatives showed the best, although modest, inhibitory activity against M. tuberculosis (17d MIC = 12.5 μg/mL, 17a 50 μg/mL). Crystal structures were determined for CYP121A1 bound

  三个系列唑哌嗪衍生物的模拟dicyclotyrosine（CYY），必需的天然底物的结核分枝杆菌的细胞色素P450 CYP121A1，制备并评价针对结合亲和力和抑制活性（MIC）的结核分枝杆菌。系列A替代了一个酚基团CYY的与C3-咪唑部分，系列B包括在系列A咪唑之前的烃链上的酮基，而C系列探索用CH替换CYY的哌啶酮环的酮基2 -咪唑或CH 2-三唑部分，以增强与CYP121A1血红素的结合相互作用。除B 10a系列外，该系列对CYP121A1显示中等至弱II型结合亲和力，其中显示了混合的I型绑定。在这三个系列中，系列C咪唑衍生物显示出对结核分枝杆菌的最佳抑制作用，尽管抑制作用适中（17d MIC = 12.5μg/ mL，17a 50μg/ mL）。确定了与系列A化合物6a和6b结合的CYP121A1的晶体结构，这些化合物显示，咪唑基团位于血红素铁的正上方，并且两个化合物的血红素铁和咪唑氮之间的键合距离为2