3-amino[2-(tert-butoxycarbonylpyridin-4-yl-amino)ethoxy]phenol | 524705-78-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-amino[2-(tert-butoxycarbonylpyridin-4-yl-amino)ethoxy]phenol
• 英文别名: tert-butyl N-[2-(3-aminophenoxy)ethyl]-N-pyridin-4-ylcarbamate
• CAS: 524705-78-0
• 化学式: C₁₈H₂₃N₃O₃
• 分子量: 329.399
• InChiKey: XVOLUYWCJPYVPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  77.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino[2-(tert-butoxycarbonylpyridin-4-yl-amino)ethoxy]phenol 在 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 4-Methyl-N-{3-[2-(pyridin-4-ylamino)-ethoxy]-phenyl}-benzenesulfonamide
  参考文献：
  名称：

  Generation of Ligand Conformations in Continuum Solvent Consistent with Protein Active Site Topology:  Application to Thrombin

  摘要：

  Using the crystal structure of an inhibitor complexed with the serine protease thrombin (PDB code 1UVT) and the functional group definitions contained within the Catalyst software, a representation of the enzyme's active site was produced (structure-based pharmacophore model). A training set of 16 homologous non-peptide inhibitors whose conformations had been generated in continuum solvent (MacroModel) and clustered into conformational. families (XCluster) was regressed against this pharmacophore so as to obtain a 3D-QSAR model. To test the robustness of the resulting QSAR model, the synthesis of a series of non-peptide thrombin inhibitors based on arylsuphonyl derivatives of an aminophenol ring linked to a pyridyl-based S1 binding group was undertaken. These compounds served as a test set (20-24). The crystal structure for the novel symmetrical disulfonyl compound 24, in complex with thrombin, has been solved. Its calculated binding mode is in general agreement with the crystallographically observed one, and the predicted K-i value is in close accord with the experimental value.

  DOI：

  10.1021/jm021028j
• 作为产物：
  描述：

  4-(叔丁氧羰基氨基)吡啶 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 79.0h， 生成 3-amino[2-(tert-butoxycarbonylpyridin-4-yl-amino)ethoxy]phenol
  参考文献：
  名称：

  Generation of Ligand Conformations in Continuum Solvent Consistent with Protein Active Site Topology:  Application to Thrombin

  摘要：

  Using the crystal structure of an inhibitor complexed with the serine protease thrombin (PDB code 1UVT) and the functional group definitions contained within the Catalyst software, a representation of the enzyme's active site was produced (structure-based pharmacophore model). A training set of 16 homologous non-peptide inhibitors whose conformations had been generated in continuum solvent (MacroModel) and clustered into conformational. families (XCluster) was regressed against this pharmacophore so as to obtain a 3D-QSAR model. To test the robustness of the resulting QSAR model, the synthesis of a series of non-peptide thrombin inhibitors based on arylsuphonyl derivatives of an aminophenol ring linked to a pyridyl-based S1 binding group was undertaken. These compounds served as a test set (20-24). The crystal structure for the novel symmetrical disulfonyl compound 24, in complex with thrombin, has been solved. Its calculated binding mode is in general agreement with the crystallographically observed one, and the predicted K-i value is in close accord with the experimental value.

  DOI：

  10.1021/jm021028j

文献信息

• Generation of Ligand Conformations in Continuum Solvent Consistent with Protein Active Site Topology:  Application to Thrombin
  作者：Paulette A. Greenidge、Sandrine A. M. Mérette、Richard Beck、Guy Dodson、Christopher A. Goodwin、Michael F. Scully、John Spencer、Jörg Weiser、John J. Deadman

  DOI：10.1021/jm021028j

  日期：2003.4.1

  Using the crystal structure of an inhibitor complexed with the serine protease thrombin (PDB code 1UVT) and the functional group definitions contained within the Catalyst software, a representation of the enzyme's active site was produced (structure-based pharmacophore model). A training set of 16 homologous non-peptide inhibitors whose conformations had been generated in continuum solvent (MacroModel) and clustered into conformational. families (XCluster) was regressed against this pharmacophore so as to obtain a 3D-QSAR model. To test the robustness of the resulting QSAR model, the synthesis of a series of non-peptide thrombin inhibitors based on arylsuphonyl derivatives of an aminophenol ring linked to a pyridyl-based S1 binding group was undertaken. These compounds served as a test set (20-24). The crystal structure for the novel symmetrical disulfonyl compound 24, in complex with thrombin, has been solved. Its calculated binding mode is in general agreement with the crystallographically observed one, and the predicted K-i value is in close accord with the experimental value.