1-(2-hydroxy-5-methylphenyl)-3-(4-fluorophenyl)propane-1,3-dione | 332103-26-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 1-(2-hydroxy-5-methylphenyl)-3-(4-fluorophenyl)propane-1,3-dione
• 英文别名: 1-(4-fluorophenyl)-3-(2-hydroxy-5-methylphenyl)propane-1,3-dione；1-(4-Fluorophenyl)-3-(2-hydroxy-5-methylphenyl)-1,3-propanedione
• CAS: 332103-26-1
• 化学式: C₁₆H₁₃FO₃
• 分子量: 272.276
• InChiKey: XHBQVCVRNFUZAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-hydroxy-5-methylphenyl)-3-(4-fluorophenyl)propane-1,3-dione 在 吡啶 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-(4-fluorophenyl)-3-(4-hydroxybenzyl)-7-methylchromeno[2,3-c]pyrrol-9(2H)-one
  参考文献：
  名称：

  Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure

  摘要：

  Phosphodiesterase-5 (PDE5) inhibitors have been approved for the treatment of erectile dysfunction and pulmonary hypertension, but enthusiasm on discovery of PDE5 inhibitors continues for their potential new applications. Reported here is discovery of a series of new PDE5 inhibitors by structure-based design, molecular docking, chemical synthesis, and enzymatic characterization. The best compound, 3(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one (57), has an IC50 of 17 nM against the PDE5 catalytic domain and good selectivity over other PDE families. The crystal structure of the PDE5 catalytic domain in complex with 57 was determined at 2 angstrom resolution and showed that 57 occupies the same pocket as other PDE5 inhibitors, but has a different binding pattern in detail. On the basis of the binding pattern of 57, a novel scaffold can be proposed as a candidate of PDE inhibitors. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2014.02.013
• 作为产物：
  描述：

  (2-Acetyl-4-methylphenyl) 4-fluorobenzoate 在 吡啶 、 potassium hydroxide 作用下， 以2.36 g的产率得到1-(2-hydroxy-5-methylphenyl)-3-(4-fluorophenyl)propane-1,3-dione
  参考文献：
  名称：

  Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure

  摘要：

  Phosphodiesterase-5 (PDE5) inhibitors have been approved for the treatment of erectile dysfunction and pulmonary hypertension, but enthusiasm on discovery of PDE5 inhibitors continues for their potential new applications. Reported here is discovery of a series of new PDE5 inhibitors by structure-based design, molecular docking, chemical synthesis, and enzymatic characterization. The best compound, 3(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one (57), has an IC50 of 17 nM against the PDE5 catalytic domain and good selectivity over other PDE families. The crystal structure of the PDE5 catalytic domain in complex with 57 was determined at 2 angstrom resolution and showed that 57 occupies the same pocket as other PDE5 inhibitors, but has a different binding pattern in detail. On the basis of the binding pattern of 57, a novel scaffold can be proposed as a candidate of PDE inhibitors. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2014.02.013