(4R,5S,6S,7R)-5,6-bis(2-methoxyethoxymethoxy)-4,7-bis(phenoxymethyl)-1,3-diazepan-2-one | 185450-13-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4R,5S,6S,7R)-5,6-bis(2-methoxyethoxymethoxy)-4,7-bis(phenoxymethyl)-1,3-diazepan-2-one
• CAS: 185450-13-9
• 化学式: C₂₇H₃₈N₂O₉
• 分子量: 534.607
• InChiKey: IOUAKHXJHXULBZ-XPGKHFPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  38
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (4R,5S,6S,7R)-5,6-bis(2-methoxyethoxymethoxy)-4,7-bis(phenoxymethyl)-1,3-diazepan-2-one 在 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 AHA001
  参考文献：
  名称：

  Cyclic HIV-1 Protease Inhibitors Derived from Mannitol:  Synthesis, Inhibitory Potencies, and Computational Predictions of Binding Affinities

  摘要：

  Ten C-2-symmetric cyclic urea and sulfamide derivatives have been synthesized from L-mannonic gamma-lactone and D-mannitol. The results of experimental measurement of their inhibitory potencies against HIV-1 protease were compared to calculated free energies of binding derived from molecular dynamics (MD) simulations. The compounds were selected, firstly, to enable elucidation of the role of stereochemistry for binding affinity (1a-d) and, secondly, to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity (la and 2-5). Thirdly, compounds with hydrogen bond-accepting or -donating groups attached to the phenyl groups in the P2 and P2' side chains (6 and 7) were selected. Binding free energies were estimated by a linear response method, whose predictive power for estimating binding affinities from MD simulations was demonstrated.

  DOI：

  10.1021/jm960728j
• 作为产物：
  描述：

  2,5-diazido-3,4-O-isopropylidene-1,6-di-O-phenyl-2,5-dideoxy-D-iditol 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydride 作用下， 以 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 4.25h， 生成 (4R,5S,6S,7R)-5,6-bis(2-methoxyethoxymethoxy)-4,7-bis(phenoxymethyl)-1,3-diazepan-2-one
  参考文献：
  名称：

  Cyclic HIV-1 Protease Inhibitors Derived from Mannitol:  Synthesis, Inhibitory Potencies, and Computational Predictions of Binding Affinities

  摘要：

  Ten C-2-symmetric cyclic urea and sulfamide derivatives have been synthesized from L-mannonic gamma-lactone and D-mannitol. The results of experimental measurement of their inhibitory potencies against HIV-1 protease were compared to calculated free energies of binding derived from molecular dynamics (MD) simulations. The compounds were selected, firstly, to enable elucidation of the role of stereochemistry for binding affinity (1a-d) and, secondly, to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity (la and 2-5). Thirdly, compounds with hydrogen bond-accepting or -donating groups attached to the phenyl groups in the P2 and P2' side chains (6 and 7) were selected. Binding free energies were estimated by a linear response method, whose predictive power for estimating binding affinities from MD simulations was demonstrated.

  DOI：

  10.1021/jm960728j