1-(4-(2-(4-甲基哌嗪-1-基)乙氧基)苯基)丙烷-1-酮 | 1004027-02-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(4-(2-(4-甲基哌嗪-1-基)乙氧基)苯基)丙烷-1-酮
• 英文名称: 1-(4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)propan-1-one
• 英文别名: 1-[4-[2-(4-Methylpiperazin-1-yl)ethoxy]phenyl]propan-1-one
• CAS: 1004027-02-4
• 化学式: C₁₆H₂₄N₂O₂
• 分子量: 276.379
• InChiKey: REHWMFIHOABAAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4,5-二氢-4,4-二甲基-2-噁唑)苯胺 、 1-(4-(2-(4-甲基哌嗪-1-基)乙氧基)苯基)丙烷-1-酮 在 三氟甲磺酸 作用下， 以 正丁醇 为溶剂， 以48%的产率得到3-methyl-2-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-1H-quinolin-4-one
  参考文献：
  名称：

  Identification, Design and Biological Evaluation of Heterocyclic Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2)

  摘要：

  Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the enzyme and whole cell P. falciparum (IC50 = 15 nM PfNDH2; IC50 = 54 nM (3D7 strain of P. falciparum) with notable oral activity of ED50/ED90 of 1.87/4.72 mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogues in this series also demonstrate nanomolar activity against the bc(1) complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies.

  DOI：

  10.1021/jm201184h
• 作为产物：
  描述：

  1-(2-氯乙基)-4-甲基哌嗪二盐酸盐 、 4-羟基苯丙酮 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 6.0h， 以60%的产率得到1-(4-(2-(4-甲基哌嗪-1-基)乙氧基)苯基)丙烷-1-酮
  参考文献：
  名称：

  Identification, Design and Biological Evaluation of Heterocyclic Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2)

  摘要：

  Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the enzyme and whole cell P. falciparum (IC50 = 15 nM PfNDH2; IC50 = 54 nM (3D7 strain of P. falciparum) with notable oral activity of ED50/ED90 of 1.87/4.72 mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogues in this series also demonstrate nanomolar activity against the bc(1) complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies.

  DOI：

  10.1021/jm201184h