(S)-tert-butyl 3-benzyl-1-(4-cyclohexylbenzyl)-5-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-8-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (S)-tert-butyl 3-benzyl-1-(4-cyclohexylbenzyl)-5-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-8-carboxylate
• 英文别名: tert-butyl (3S)-3-benzyl-1-[(4-cyclohexylphenyl)methyl]-5-methyl-2-oxo-3H-1,4-benzodiazepine-8-carboxylate
• 化学式: C₃₅H₄₀N₂O₃
• 分子量: 536.714
• InChiKey: ZMHQDQLYROTXBM-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 3-benzyl-1-(4-cyclohexylbenzyl)-5-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-8-carboxylate 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 4.0h， 以98%的产率得到(S)-3-benzyl-1-(4-cyclohexylbenzyl)-5-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-8-carboxylic acid trifluoroacetic acid salt
  参考文献：
  名称：

  Synthetic, structural mimetics of the β-hairpin flap of HIV-1 protease inhibit enzyme function

  摘要：

  Small-molecule mimetics of the beta-hairpin flap of HIV-1 protease (HIV-1 PR) were designed based on a 1,4-benzodiazepine scaffold as a strategy to interfere with the flap-flap protein-protein interaction, which functions as a gated mechanism to control access to the active site. Michaelis-Menten kinetics suggested our small-molecules are competitive inhibitors, which indicates the mode of inhibition is through binding the active site or sterically blocking access to the active site and preventing flap closure, as designed. More generally, a new bioactive scaffold for HIV-1PR inhibition has been discovered, with the most potent compound inhibiting the protease with a modest K-i of 11 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.002
• 作为产物：
  描述：

  对乙基苯甲酸 在 N-甲基吗啉 、 chromium(VI) oxide 、 4-二甲氨基吡啶 、 硫酸 、 palladium on carbon 、 氢气 、 硝酸 、 potassium carbonate 、 高碘酸 、 二乙胺 、 N,N'-二环己基碳二亚胺 、 氯甲酸异丁酯 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 47.5h， 生成 (S)-tert-butyl 3-benzyl-1-(4-cyclohexylbenzyl)-5-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-8-carboxylate
  参考文献：
  名称：

  Synthetic, structural mimetics of the β-hairpin flap of HIV-1 protease inhibit enzyme function

  摘要：

  Small-molecule mimetics of the beta-hairpin flap of HIV-1 protease (HIV-1 PR) were designed based on a 1,4-benzodiazepine scaffold as a strategy to interfere with the flap-flap protein-protein interaction, which functions as a gated mechanism to control access to the active site. Michaelis-Menten kinetics suggested our small-molecules are competitive inhibitors, which indicates the mode of inhibition is through binding the active site or sterically blocking access to the active site and preventing flap closure, as designed. More generally, a new bioactive scaffold for HIV-1PR inhibition has been discovered, with the most potent compound inhibiting the protease with a modest K-i of 11 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.002