(E)-4-(3,5-Dibromo-2-hydroxy-phenyl)-but-3-en-2-one | 124771-56-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-4-(3,5-Dibromo-2-hydroxy-phenyl)-but-3-en-2-one
• 英文别名: 4-(3,5-dibromo-2-hydroxyphenyl)but-3-en-2-one
• CAS: 124771-56-8
• 化学式: C₁₀H₈Br₂O₂
• 分子量: 319.98
• InChiKey: LARPECBKFZRKRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  14.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  37.3
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (E)-4-(3,5-Dibromo-2-hydroxy-phenyl)-but-3-en-2-one 在 4-二甲氨基吡啶 、 一水合肼 、 三乙胺 、 potassium iodide 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 生成 1-(5-(3,5-dibromo-2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone-2-(4-hydroxyethyl)piperazidine
  参考文献：
  名称：

  Design and synthesis of novel 2-pyrazoline-1-ethanone derivatives as selective MAO inhibitors

  摘要：

  Thirty seven novel 2-pyrazoline-1-ethanone derivatives were designed, synthesized and evaluated as selective hMAO inhibitors. Among them, compounds 7h (IC50 = 2.40 mu M) and 12c (IC50 = 2.00 mu M) exhibited best inhibitory activity and selectivity against hMAO-A, surpassing that of the positive control Clorgyline (IC50 = 2.76 mu M). Based on selective activity of hMAO-A, SAR analysis showed that the order of N1 substituent contribution was bromo (3) > piperidinyl (4) > morpholinyl (5) > imidazolyl (6), and compounds with electron-withdrawing substituents (-F, -Cl) at C3 or C5 phenyl ring of 2-pyrazoline nucleus dedicated stronger MAO-A inhibitory activity. Molecular docking showed that compounds 7h and 12c were nicely bound to hMAO-A via two hydrogen bonds (SER209, GLU216), one Pi-Pi interaction and three hydrogen bonds (SER209, GLU216, TYR69), one Sigma-Pi interaction, respectively. In addition, the substituent at C3 position of 2-pyrazoline with the N1 acetyl has little effect on MAO-A inhibitory activity. These data support further studies to assess rational design of more efficiently selective hMAO inhibitors in the future. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.010
• 作为产物：
  描述：

  3,5-二溴水杨醛 、 丙酮 在 sodium hydroxide 作用下， 生成 (E)-4-(3,5-Dibromo-2-hydroxy-phenyl)-but-3-en-2-one
  参考文献：
  名称：

  三环吡唑并[1,5-c] [1,3]苯并恶嗪-5（5H）-1骨架作为BuChE选择性抑制剂的设计，合成及生物学评价。

  摘要：

  基于三环支架作为丁酰胆碱酯酶（BuChE）抑制剂的结构分析，设计，合成了一系列吡唑并[1,5-c] [1,3]苯并恶嗪-5（5H）-one衍生物，并对其乙酰胆碱酯酶进行了评估（ AChE）和BuChE抑制活性。具有5-羰基和7-或/和9-卤素取代基的化合物显示出潜在的BuChE抑制活性，其中化合物6a，6c和6g显示出最佳的BuChE抑制作用（IC50分别为1.06、1.63和1.63 µM）。结构活性关系表明5-羰基和卤素取代基显着影响BuChE活性。发现化合物6a和6g无毒，亲脂并显示出显着的神经保护活性和对BuChE的混合型抑制作用（Ki分别为7.46和3.09 µM）。

  DOI：

  10.1080/14756366.2018.1488696

文献信息

• Tricyclic pyrazolo[1,5- d ][1,4]benzoxazepin-5(6H)-one scaffold derivatives: Synthesis and biological evaluation as selective BuChE inhibitors
  作者：Shi-Chao Chen、Guo-Liang Qiu、Bo Li、Jing-Bo Shi、Xin-Hua Liu、Wen-Jian Tang

  DOI：10.1016/j.ejmech.2018.02.002

  日期：2018.3

  roles in treatment of patients with advanced Alzheimer's disease (AD). A series of tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one derivatives were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Some derivatives showed selective BuChE inhibitory activity, which was influenced by the volumes of the substituted groups at the C6 position and

  BuChE抑制剂在晚期阿尔茨海默氏病（AD）患者的治疗中起着重要作用。合成了一系列三环吡唑并[1,5- d ] [1,4]苯并x庚因-5（6H）-一衍生物，并将其评估为乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制剂。一些衍生物表现出选择性的BuChE抑制活性，这受三环支架的C6位取代基的体积和苯环上卤素取代基的体积的影响。其中，具有二卤素和6-乙基取代基的化合物3f和3o表现出最强的活性（IC 50分别 为2.95、2.04μM和对BuChE的混合型，非竞争性抑制）。Eutomer （6 R）-3o比（6 S）-3o表现出更好的BuChE抑制活性。化合物3o显示出无毒，良好的ADMET特性和显着的神经保护活性。对接研究揭示了靶酶活性位点内的相同结合方向。化合物3o通过三个氢键，一个烷基相互作用和三个Pi-烷基相互作用与BuChE很好地结合。选择性BuChE抑制剂在进行性神经退行性疾病中具有潜在用途。
• Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo
  作者：Yang Wang、Fei Xiong Cheng、Xiao Long Yuan、Wen Jian Tang、Jing Bo Shi、Chen Zhong Liao、Xin Hua Liu

  DOI：10.1016/j.ejmech.2016.02.009

  日期：2016.4

  It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound 13i exhibited the most potent inhibitory activity against telomerase with an IC50 value of 0.98 mu M. In vivo evaluation results indicated that compound 13i could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Reddy; Mogilaiah; Sreenivasulu, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1989, vol. 28, # 4, p. 362 - 364
  作者：Reddy、Mogilaiah、Sreenivasulu

  DOI：——

  日期：——
• Design and synthesis of novel 2-methyl-4,5-substitutedbenzo[f]-3,3a,4,5-tetrahydro-pyrazolo[1,5-d][1,4]oxazepin-8(7H)-one derivatives as telomerase inhibitors
  作者：Xin-Hua Liu、Ying-Ming Jia、Bao-An Song、Zhi-xiang Pang、Song Yang

  DOI：10.1016/j.bmcl.2012.11.101

  日期：2013.2

  Eight novel 4,5-tetrahydropyrazolo[1,5-d][1,4] oxazepine derivatives have been synthesized and purified to be screened for anticancer activity. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 4a showed the most potent inhibitory activity with IC50 value at 0.78 +/- 0.22 mu M. Western blot assays showed that compounds 4a and 4b could inhibit expression of Cyclin D1, TERT, phospho-AKT and PI3K/AKT pathway. (c) 2012 Elsevier Ltd. All rights reserved.
• Novel coumarin-dihydropyrazole thio-ethanone derivatives: Design, synthesis and anticancer activity
  作者：Xiao-Qin Wu、Cheng Huang、Ying-Ming Jia、Bao-An Song、Jun Li、Xin-Hua Liu

  DOI：10.1016/j.ejmech.2013.06.014

  日期：2014.3

  A series novel 1-(3-substituted-5-pheny1-4,5-dihydropyrazol-1-y1)-2-thio-ethanone derivatives as potential telomerase inhibitors were designed and synthesized. The bioassays demonstrated that compounds 4a, 4f, 4j and 7b, 7d occupied high antiproliferative activity against SGC-7901, MGC-803, Bcap-37 and HEPG-2 cell lines. By a modified TRAP assay, some title compounds were tested against telomerase, and compound 4f showed the most potent inhibitory activity with IC50 value at 0.92 +/- 0.09 mu M. The mechanism of antitumor action indicated that title compounds 4f and 7b could suppress cell proliferation through inducing cell cycle arrest in G0/G1 phase. (C) 2013 Elsevier Masson SAS. All rights reserved.