(4R,5S,6S,7R)-1,3-bis[[4-(methoxycarbonyl)phenyl]methyl]-5,6-bis[(2-methoxyethoxy)methoxy]-4,7-bis(phenoxymethyl)-1,3-diazepan-2-one | 185450-19-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4R,5S,6S,7R)-1,3-bis[[4-(methoxycarbonyl)phenyl]methyl]-5,6-bis[(2-methoxyethoxy)methoxy]-4,7-bis(phenoxymethyl)-1,3-diazepan-2-one
• 英文别名: methyl 4-[[(4R,5S,6S,7R)-3-[(4-methoxycarbonylphenyl)methyl]-5,6-bis(2-methoxyethoxymethoxy)-2-oxo-4,7-bis(phenoxymethyl)-1,3-diazepan-1-yl]methyl]benzoate
• CAS: 185450-19-5
• 化学式: C₄₅H₅₄N₂O₁₃
• 分子量: 830.929
• InChiKey: ACDXGJGDGIMBNZ-GLGKVNTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  60
• 可旋转键数：
  26
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  150
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (4R,5S,6S,7R)-1,3-bis[[4-(methoxycarbonyl)phenyl]methyl]-5,6-bis[(2-methoxyethoxy)methoxy]-4,7-bis(phenoxymethyl)-1,3-diazepan-2-one 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以92%的产率得到(4R,5S,6S,7R)-1,3-bis[[4-(methoxycarbonyl)phenyl]methyl]-4,7-bis(phenoxymethyl)-5,6-dihydroxy-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
• 作为产物：
  描述：

  2,5-diazido-3,4-bis-O-[(2-methoxyethoxy)methyl]-1,6-di-O-phenyl-2,5-dideoxy-d-iditol 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (4R,5S,6S,7R)-1,3-bis[[4-(methoxycarbonyl)phenyl]methyl]-5,6-bis[(2-methoxyethoxy)methoxy]-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

文献信息

• Cyclic HIV-1 Protease Inhibitors Derived from Mannitol:  Synthesis, Inhibitory Potencies, and Computational Predictions of Binding Affinities
  作者：Johan Hultén、Nicholas M. Bonham、Ulrika Nillroth、Tomas Hansson、Guido Zuccarello、Abderrahim Bouzide、Johan Åqvist、Björn Classon、U. Helena Danielson、Anders Karlén、Ingemar Kvarnström、Bertil Samuelsson、Anders Hallberg

  DOI：10.1021/jm960728j

  日期：1997.3.1

  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.