1-(4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)propan-1-one | 1361968-05-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)propan-1-one
• 英文别名: 1-[4-(Oxan-4-yloxy)phenyl]propan-1-one
• CAS: 1361968-05-9
• 化学式: C₁₄H₁₈O₃
• 分子量: 234.295
• InChiKey: MYIPRWVJTHGZRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 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：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)propan-1-one 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 生成 3-methyl-2-(4-tetrahydropyran-4-yloxyphenyl)-1H-1,8-naphthyridin-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：

  四氢吡喃-4-醇 、 4-羟基苯丙酮 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以52%的产率得到1-(4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)propan-1-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