1-(5-(3,5-dibromo-2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone-2-(4-hydroxyl)piperidine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(5-(3,5-dibromo-2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone-2-(4-hydroxyl)piperidine
• 英文别名: 1-[3-(3,5-Dibromo-2-hydroxyphenyl)-5-methyl-3,4-dihydropyrazol-2-yl]-2-(4-hydroxypiperidin-1-yl)ethanone；1-[3-(3,5-dibromo-2-hydroxyphenyl)-5-methyl-3,4-dihydropyrazol-2-yl]-2-(4-hydroxypiperidin-1-yl)ethanone
• 化学式: C₁₇H₂₁Br₂N₃O₃
• 分子量: 475.18
• InChiKey: CEDZPYRSEWOHNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  76.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  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-hydroxyl)piperidine
  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

文献信息

• Design and synthesis of novel 2-pyrazoline-1-ethanone derivatives as selective MAO inhibitors
  作者：Xu Tong、Rui Chen、Tong-Tian Zhang、Yan Han、Wen-Jian Tang、Xin-Hua Liu

  DOI：10.1016/j.bmc.2014.12.010

  日期：2015.2

  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.