2,6-bis(4-(N-hydroxycarbamimidoyl)phenoxy)-3-(4-fluorophenylsulphonamido)pyridine | 1467746-26-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,6-bis(4-(N-hydroxycarbamimidoyl)phenoxy)-3-(4-fluorophenylsulphonamido)pyridine
• CAS: 1467746-26-4
• 化学式: C₂₅H₂₁FN₆O₆S
• 分子量: 552.543
• InChiKey: ZVWIPIRMXCYEDU-UHFFFAOYSA-N

物化性质

• 沸点：
  706.1±70.0 °C(predicted)
• 密度：
  1.52±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  39.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  194.74
• 氢给体数：
  5.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2,6-bis(4-(N-hydroxycarbamimidoyl)phenoxy)-3-(4-fluorophenylsulphonamido)pyridine 在 溶剂黄146 、 锌 作用下， 生成 4,4'-((3-(4-fluorophenylsulfonamido)pyridine-2,6-diyl)bis(oxy))dibenzimidamide
  参考文献：
  名称：

  Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors

  摘要：

  Matriptase belongs to trypsin-like serine proteases involved in matrix remodeling/degradation, growth regulation, survival, motility, and cell morphogenesis. Herein, we report a structure-based approach, which led to the discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as potent and selective matriptase inhibitors. Co-crystal structures of selected compounds in complex with matriptase supported compound designing. Additionally, WaterMap analyses indicated the possibility of occupying a distinct pocket within the catalytic domain, exploration of which resulted in >100-fold improvement in potency. Co-crystal structure of 10 with matriptase revealed critical interactions leading to potent target inhibition and selectivity against other senile proteases.

  DOI：

  10.1021/ml400213v
• 作为产物：
  描述：

  2,6-二氯-3-硝基吡啶 在 盐酸羟胺 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.17h， 生成 2,6-bis(4-(N-hydroxycarbamimidoyl)phenoxy)-3-(4-fluorophenylsulphonamido)pyridine
  参考文献：
  名称：

  Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors

  摘要：

  Matriptase belongs to trypsin-like serine proteases involved in matrix remodeling/degradation, growth regulation, survival, motility, and cell morphogenesis. Herein, we report a structure-based approach, which led to the discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as potent and selective matriptase inhibitors. Co-crystal structures of selected compounds in complex with matriptase supported compound designing. Additionally, WaterMap analyses indicated the possibility of occupying a distinct pocket within the catalytic domain, exploration of which resulted in >100-fold improvement in potency. Co-crystal structure of 10 with matriptase revealed critical interactions leading to potent target inhibition and selectivity against other senile proteases.

  DOI：

  10.1021/ml400213v