(2R,4S,5S)-2-benzyl-5-{[(tert-butoxy)carbonyl]amino}-4-[(tertbutyldimethylsilyl)oxy]-6-methylheptanoic acid | 869494-32-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (2R,4S,5S)-2-benzyl-5-{[(tert-butoxy)carbonyl]amino}-4-[(tertbutyldimethylsilyl)oxy]-6-methylheptanoic acid
• 英文别名: (2R,4S,5S)-2-benzyl-4-[tert-butyl(dimethyl)silyl]oxy-6-methyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]heptanoic acid
• CAS: 869494-32-6
• 化学式: C₂₆H₄₅NO₅Si
• 分子量: 479.733
• InChiKey: XRKMQYGDGJLHTC-FSSWDIPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.26
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,4S,5S)-2-benzyl-5-{[(tert-butoxy)carbonyl]amino}-4-[(tertbutyldimethylsilyl)oxy]-6-methylheptanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.84h， 生成 ethyl (E,4S)-4-[[(2R,4S,5S)-2-benzyl-4-[tert-butyl(dimethyl)silyl]oxy-6-methyl-5-[(5-methyl-1,2-oxazole-3-carbonyl)amino]heptanoyl]amino]-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate
  参考文献：
  名称：

  Design and Synthesis of Peptidomimetic Severe Acute Respiratory Syndrome Chymotrypsin-like Protease Inhibitors

  摘要：

  Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.

  DOI：

  10.1021/jm050548m
• 作为产物：
  描述：

  tert-butyl ((S)-2-methyl-1-((R)-5-oxotetrahydrofuran-2-yl)propyl)carbamate 在 咪唑 、 lithium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.84h， 生成 (2R,4S,5S)-2-benzyl-5-{[(tert-butoxy)carbonyl]amino}-4-[(tertbutyldimethylsilyl)oxy]-6-methylheptanoic acid
  参考文献：
  名称：

  Design and Synthesis of Peptidomimetic Severe Acute Respiratory Syndrome Chymotrypsin-like Protease Inhibitors

  摘要：

  Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.

  DOI：

  10.1021/jm050548m

文献信息

• Efficient Entropy‐Driven Inhibition of Dipeptidyl Peptidase III by Hydroxyethylene Transition‐State Peptidomimetics
  作者：Jakov Ivkovic、Shalinee Jha、Christian Lembacher‐Fadum、Johannes Puschnig、Prashant Kumar、Viktoria Reithofer、Karl Gruber、Peter Macheroux、Rolf Breinbauer

  DOI：10.1002/chem.202102204

  日期：2021.10.7

  from the closing binding cleft. Here, the design, synthesis and biophysical characterization of peptidomimetic inhibitors is reported, using for the first time an hydroxyethylene transition-state mimetic for a metalloprotease. Efficient routes for the synthesis of both stereoisomers of the pseudopeptide core were developed, which allowed the synthesis of peptidomimetic inhibitors mimicking the VVYPW-motif

  二肽基肽酶 III (DPP3) 是一种普遍表达的锌依赖性蛋白酶，在调节内源性肽激素（如脑啡肽或血管紧张素）中起重要作用。在之前的生物物理研究中，可以表明底物结合是由大熵贡献驱动的，这是由于水分子从闭合的结合裂缝中释放出来的。在这里，报告了拟肽抑制剂的设计、合成和生物物理表征，首次使用金属蛋白酶的羟基乙烯过渡态模拟物。开发了合成假肽核心的两种立体异构体的有效途径，这允许合成模拟 tynorphin 的 VVYPW 基序的拟肽抑制剂。最好的抑制剂在低 μM 范围内抑制 DPP3。通过 ITC 测量和 X 射线晶体学的生物物理表征证实了不寻常的熵驱动结合模式。稳定性测定证明了这些抑制剂所需的稳定性，可有效抑制小鼠脑匀浆中的 DPP3。
• Design and Synthesis of Peptidomimetic Severe Acute Respiratory Syndrome Chymotrypsin-like Protease Inhibitors
  作者：Arun K. Ghosh、Kai Xi、Kiira Ratia、Bernard D. Santarsiero、Wentao Fu、Brian H. Harcourt、Paul A. Rota、Susan C. Baker、Michael E. Johnson、Andrew D. Mesecar

  DOI：10.1021/jm050548m

  日期：2005.11.1

  Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.