1-(4-(4-(methoxymethoxy)phenyl)piperazin-1-yl)ethan-1-one | 1246819-45-3

• 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-(4-(4-(methoxymethoxy)phenyl)piperazin-1-yl)ethan-1-one
• 英文别名: 1-Acetyl-4-[4-(methoxymethoxy)phenyl]piperazine；1-[4-[4-(methoxymethoxy)phenyl]piperazin-1-yl]ethanone
• CAS: 1246819-45-3
• 化学式: C₁₄H₂₀N₂O₃
• 分子量: 264.324
• InChiKey: JGTPWPCAOYUPAB-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于氯仿、二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-(4-(methoxymethoxy)phenyl)piperazin-1-yl)ethan-1-one 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以91%的产率得到1-(4-(methoxymethoxy)phenyl)piperazine
  参考文献：
  名称：

  A_2B Adenosine Receptor Antagonists with Picomolar Potency

  摘要：

  The A(2B) adenosine receptor (A(2B)AR) was proposed as a novel target for the (immuno)therapy of cancer since A(2B)AR blockade results in antiproliferative, antiangiogenic, antimetastatic, and immunostimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established, which facilitated the synthesis of the target compounds. Many of the new compounds exhibited subnanomolar affinity for the A(2B)AR combined with high selectivity. Functional groups were introduced, which will allow the attachment of dyes and other reporter groups. 8-(4((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A(2B)-antagonist (K-i 0.0835 nM, K-B 0.0598 nM, human A(2B)AR) with >10 000-fold selectivity versus all other AR subtypes. It was similarly potent and selective at the mouse A(2B)AR, making it a promising tool for preclinical studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.

  DOI：

  10.1021/acs.jmedchem.9b00071
• 作为产物：
  描述：

  氯甲基甲基醚 、 1-乙酰基-4-(4-羟基苯基)哌嗪 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以73%的产率得到1-(4-(4-(methoxymethoxy)phenyl)piperazin-1-yl)ethan-1-one
  参考文献：
  名称：

  A_2B Adenosine Receptor Antagonists with Picomolar Potency

  摘要：

  The A(2B) adenosine receptor (A(2B)AR) was proposed as a novel target for the (immuno)therapy of cancer since A(2B)AR blockade results in antiproliferative, antiangiogenic, antimetastatic, and immunostimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established, which facilitated the synthesis of the target compounds. Many of the new compounds exhibited subnanomolar affinity for the A(2B)AR combined with high selectivity. Functional groups were introduced, which will allow the attachment of dyes and other reporter groups. 8-(4((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A(2B)-antagonist (K-i 0.0835 nM, K-B 0.0598 nM, human A(2B)AR) with >10 000-fold selectivity versus all other AR subtypes. It was similarly potent and selective at the mouse A(2B)AR, making it a promising tool for preclinical studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.

  DOI：

  10.1021/acs.jmedchem.9b00071

文献信息

• A_2B Adenosine Receptor Antagonists with Picomolar Potency
  作者：Jie Jiang、Catharina Julia Seel、Ahmed Temirak、Vigneshwaran Namasivayam、Antonella Arridu、Jakub Schabikowski、Younis Baqi、Sonja Hinz、Jörg Hockemeyer、Christa E. Müller

  DOI：10.1021/acs.jmedchem.9b00071

  日期：2019.4.25

  The A(2B) adenosine receptor (A(2B)AR) was proposed as a novel target for the (immuno)therapy of cancer since A(2B)AR blockade results in antiproliferative, antiangiogenic, antimetastatic, and immunostimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established, which facilitated the synthesis of the target compounds. Many of the new compounds exhibited subnanomolar affinity for the A(2B)AR combined with high selectivity. Functional groups were introduced, which will allow the attachment of dyes and other reporter groups. 8-(4((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A(2B)-antagonist (K-i 0.0835 nM, K-B 0.0598 nM, human A(2B)AR) with >10 000-fold selectivity versus all other AR subtypes. It was similarly potent and selective at the mouse A(2B)AR, making it a promising tool for preclinical studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.