<9(S),12(S)>-α,α-difluoro-β-hydroxy-9-(1-methylethyl)-4,7,10-trioxo-N-(phenylmethyl)-2-oxa-5,8,11-triazabicyclo<12,2,2>octadeca-14,16,17-triene-12-propanamide | 158342-63-3

• 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: <9(S),12(S)>-α,α-difluoro-β-hydroxy-9-(1-methylethyl)-4,7,10-trioxo-N-(phenylmethyl)-2-oxa-5,8,11-triazabicyclo<12,2,2>octadeca-14,16,17-triene-12-propanamide
• 英文别名: (3S)-N-benzyl-2,2-difluoro-3-hydroxy-3-[(9S,12S)-4,7,10-trioxo-9-propan-2-yl-2-oxa-5,8,11-triazabicyclo[12.2.2]octadeca-1(16),14,17-trien-12-yl]propanamide
• CAS: 158342-63-3
• 化学式: C₂₇H₃₂F₂N₄O₆
• 分子量: 546.571
• InChiKey: MIPPLRCAPCKUOD-OYDLWJJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  <9(S),12(S)>-α,α-difluoro-β-hydroxy-9-(1-methylethyl)-4,7,10-trioxo-N-(phenylmethyl)-2-oxa-5,8,11-triazabicyclo<12,2,2>octadeca-14,16,17-triene-12-propanamide 在 戴斯-马丁氧化剂 作用下， 以 乙腈 为溶剂， 反应 96.0h， 生成 MDL 104168
  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：

  在 盐酸 、 碳酸氢钠 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 1,4-二氧六环 、 氘代二甲亚砜 、 二氯甲烷 为溶剂， 反应 146.0h， 生成 <9(S),12(S)>-α,α-difluoro-β-hydroxy-9-(1-methylethyl)-4,7,10-trioxo-N-(phenylmethyl)-2-oxa-5,8,11-triazabicyclo<12,2,2>octadeca-14,16,17-triene-12-propanamide
  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