tert-butyl ((1r,4r)-4-(2,6-bis(4-(N'-acetoxycarbamimidoyl)phenoxy)isonicotinamido)cyclohexyl)carbamate | 1467746-37-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl ((1r,4r)-4-(2,6-bis(4-(N'-acetoxycarbamimidoyl)phenoxy)isonicotinamido)cyclohexyl)carbamate
• CAS: 1467746-37-7
• 化学式: C₃₅H₄₁N₇O₉
• 分子量: 703.752
• InChiKey: PWGKGQMYWJHNGT-DIVCQZSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  51.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  228.14
• 氢给体数：
  4.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  tert-butyl ((1r,4r)-4-(2,6-bis(4-(N'-acetoxycarbamimidoyl)phenoxy)isonicotinamido)cyclohexyl)carbamate 在 盐酸 、 溶剂黄146 、 锌 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 N-((1r,4r)-4-aminocyclohexyl)-2,6-bis(4-carbamimidoylphenoxy)isonicotinamide
  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：

  ethyl 2,6-bis(4-cyanophenoxy)isonicotinate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 羟胺 、 溶剂黄146 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.17h， 生成 tert-butyl ((1r,4r)-4-(2,6-bis(4-(N'-acetoxycarbamimidoyl)phenoxy)isonicotinamido)cyclohexyl)carbamate
  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