N-(3-(2-(benzyloxy)-6-(3-(benzyloxy)phenyl)naphthalen-1-yl)phenyl)-2-fluorobenzenesulfonamide | 1365958-78-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: N-(3-(2-(benzyloxy)-6-(3-(benzyloxy)phenyl)naphthalen-1-yl)phenyl)-2-fluorobenzenesulfonamide
• CAS: 1365958-78-6
• 化学式: C₄₂H₃₂FNO₄S
• 分子量: 665.785
• InChiKey: KMIPWBYYMMVHGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.27
• 重原子数：
  49.0
• 可旋转键数：
  11.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(3-(2-(benzyloxy)-6-(3-(benzyloxy)phenyl)naphthalen-1-yl)phenyl)-2-fluorobenzenesulfonamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以71%的产率得到N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-2-fluorobenzenesulfonamide
  参考文献：
  名称：

  Lead Optimization of 17β-HSD1 Inhibitors of the (Hydroxyphenyl)naphthol Sulfonamide Type for the Treatment of Endometriosis

  摘要：

  The reduction of estrone to estradiol, the most potent estrogen in human, is catalyzed by 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1). A promising approach for the treatment of estrogen-dependent diseases is the reduction of intracellular estradiol formation by inhibition of 17 beta-HSD1. For the species-specific optimization of the (hydroxyphenyl)naphthols, a combinatorial approach was applied and enhanced by a focused synthesis that resulted in the aromatic-substituted (hydroxyphenyl)naphthol sulfonamides. Rigidification of 12 led to the 4-indolylsulfonamide 30, which is a highly active and selective human 17 beta-HSD1 inhibitor, as well as a highly potent and selective inhibitor of 17 beta-HSD1 from Callithrix jacchus. It shows no affinity to the estrogen receptors a and 9 and good intracellular activity (T47D). Thus, compound 30 shows good properties for further ADMET studies and might be a candidate for the in vivo proof of concept in C. jacchus.

  DOI：

  10.1021/jm201735j
• 作为产物：
  描述：

  2-(benzyloxy)-1,6-dibromonaphthalene 在 吡啶 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 20.0~150.0 ℃ 、150.0 kPa 条件下， 反应 148.25h， 生成 N-(3-(2-(benzyloxy)-6-(3-(benzyloxy)phenyl)naphthalen-1-yl)phenyl)-2-fluorobenzenesulfonamide
  参考文献：
  名称：

  Lead Optimization of 17β-HSD1 Inhibitors of the (Hydroxyphenyl)naphthol Sulfonamide Type for the Treatment of Endometriosis

  摘要：

  The reduction of estrone to estradiol, the most potent estrogen in human, is catalyzed by 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1). A promising approach for the treatment of estrogen-dependent diseases is the reduction of intracellular estradiol formation by inhibition of 17 beta-HSD1. For the species-specific optimization of the (hydroxyphenyl)naphthols, a combinatorial approach was applied and enhanced by a focused synthesis that resulted in the aromatic-substituted (hydroxyphenyl)naphthol sulfonamides. Rigidification of 12 led to the 4-indolylsulfonamide 30, which is a highly active and selective human 17 beta-HSD1 inhibitor, as well as a highly potent and selective inhibitor of 17 beta-HSD1 from Callithrix jacchus. It shows no affinity to the estrogen receptors a and 9 and good intracellular activity (T47D). Thus, compound 30 shows good properties for further ADMET studies and might be a candidate for the in vivo proof of concept in C. jacchus.

  DOI：

  10.1021/jm201735j