<3(S),4(S)>-2,4,5-trideoxy-4-<<2-<<<<(1,1-dimethylethoxy)carbonyl>amino>acetyl>amino>-3-methyl-1-oxobutyl>amino>-2,2-difluoro-5-<4-(2-methoxy-2-oxoethoxy)phenyl>-N-(phenylmethyl)-L-glycero-pentonamide | 158342-61-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: <3(S),4(S)>-2,4,5-trideoxy-4-<<2-<<<<(1,1-dimethylethoxy)carbonyl>amino>acetyl>amino>-3-methyl-1-oxobutyl>amino>-2,2-difluoro-5-<4-(2-methoxy-2-oxoethoxy)phenyl>-N-(phenylmethyl)-L-glycero-pentonamide
• CAS: 158342-61-1
• 化学式: C₃₃H₄₄F₂N₄O₉
• 分子量: 678.731
• InChiKey: AMTSBEVBYNWSHK-WIRXVTQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.24
• 重原子数：
  48.0
• 可旋转键数：
  16.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  181.39
• 氢给体数：
  5.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  <3(S),4(S)>-2,4,5-trideoxy-4-<<2-<<<<(1,1-dimethylethoxy)carbonyl>amino>acetyl>amino>-3-methyl-1-oxobutyl>amino>-2,2-difluoro-5-<4-(2-methoxy-2-oxoethoxy)phenyl>-N-(phenylmethyl)-L-glycero-pentonamide 在 lithium hydroxide 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 氘代二甲亚砜 、 二氯甲烷 、 水 为溶剂， 反应 76.0h， 生成 <3(S),4(S)>-2,4,5-trideoxy-4-<<2-<<<<(1,1-dimethylethoxy)carbonyl>amino>acetyl>amino>-3-methyl-1-oxobutyl>amino>-2,2-difluoro-5-<4-<2-oxo-2-(pentafluorophenoxy)ethoxy>phenyl>-N-(phenylmethyl)-L-glycero-pentonamide
  参考文献：
  名称：

  Design, Synthesis, and Conformational Analysis of a Novel Macrocyclic HIV-Protease Inhibitor

  摘要：

  Design modifications to the lead HnT-PR inhibitor 1 (MDL 73,669, K-i = 5 nM) have been postulated based on a computational model of the 1/HIV-PR complex. A novel macrocyclic inhibitor 8 (MDL 104,168) wherein the P-1 and P-3 Side chains of the original acyclic inhibitor have been joined retains good biological activity (K-i = 20 nM). NMR analysis of the precursor alcohol (S)-7 shows the conformation of the cyclic region to be very similar to that observed in the enzyme-bound 8 as determined by the computational model. Consistency of the computational model with NMR data and in vacuo molecular dynamics simulations provide the basis for postulating further modifications of the cyclic inhibitor expected to optimize its interactions with HIV-PR.

  DOI：

  10.1021/jm00048a004
• 作为产物：
  描述：

  2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile 在 N-甲基吗啉 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 1-羟基苯并三唑一水物 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 <3(S),4(S)>-2,4,5-trideoxy-4-<<2-<<<<(1,1-dimethylethoxy)carbonyl>amino>acetyl>amino>-3-methyl-1-oxobutyl>amino>-2,2-difluoro-5-<4-(2-methoxy-2-oxoethoxy)phenyl>-N-(phenylmethyl)-L-glycero-pentonamide
  参考文献：
  名称：

  Design, Synthesis, and Conformational Analysis of a Novel Macrocyclic HIV-Protease Inhibitor

  摘要：

  Design modifications to the lead HnT-PR inhibitor 1 (MDL 73,669, K-i = 5 nM) have been postulated based on a computational model of the 1/HIV-PR complex. A novel macrocyclic inhibitor 8 (MDL 104,168) wherein the P-1 and P-3 Side chains of the original acyclic inhibitor have been joined retains good biological activity (K-i = 20 nM). NMR analysis of the precursor alcohol (S)-7 shows the conformation of the cyclic region to be very similar to that observed in the enzyme-bound 8 as determined by the computational model. Consistency of the computational model with NMR data and in vacuo molecular dynamics simulations provide the basis for postulating further modifications of the cyclic inhibitor expected to optimize its interactions with HIV-PR.

  DOI：

  10.1021/jm00048a004