N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-{[(1,1-dimethylathoxy)carbonyl]amino}-4(S)-hydroxy-6-phenyl-2(R)-[3-(4-hydroxyphenyl)prop-2-en-1-yl]hexanamide

• 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: N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-{[(1,1-dimethylathoxy)carbonyl]amino}-4(S)-hydroxy-6-phenyl-2(R)-[3-(4-hydroxyphenyl)prop-2-en-1-yl]hexanamide
• 英文别名: tert-butyl N-[(E,1S,2S,4R)-1-benzyl-2-hydroxy-4-[[(1S,2R)-2-hydroxyindan-1-yl]carbamoyl]-7-(4-hydroxyphenyl)hept-6-enyl]carbamate；tert-butyl N-[(E,2S,3S,5R)-3-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamoyl]-8-(4-hydroxyphenyl)-1-phenyloct-7-en-2-yl]carbamate
• 化学式: C₃₅H₄₂N₂O₆
• 分子量: 586.728
• InChiKey: CEJZVKZLVAQAHB-XGZUOCAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  43
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  128
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(2-氯乙基)吗啉 、 N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-{[(1,1-dimethylathoxy)carbonyl]amino}-4(S)-hydroxy-6-phenyl-2(R)-[3-(4-hydroxyphenyl)prop-2-en-1-yl]hexanamide 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以32%的产率得到N-<2(R)-hydroxy-1(S)-indanyl>-5(S)-<<(1,1-dimethylathoxy)carbonyl>amino>-4(S)-hydroxy-6-phenyl-2(R)-<3-<4-(morpholinoethoxy)phenyl>prop-2-en-1-yl>hexanamide
  参考文献：
  名称：

  HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: An investigation into the role of the P1' side chain on structure-activity

  摘要：

  A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T-lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.

  DOI：

  10.1021/jm00088a004
• 作为产物：
  描述：

  4-香豆酸 在 咪唑 、 lithium hydroxide 、 四丁基氟化铵 、 sodium ethanolate 、 三溴化磷 、 二异丁基氢化铝 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醚 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 171.33h， 生成 N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-{[(1,1-dimethylathoxy)carbonyl]amino}-4(S)-hydroxy-6-phenyl-2(R)-[3-(4-hydroxyphenyl)prop-2-en-1-yl]hexanamide
  参考文献：
  名称：

  HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: An investigation into the role of the P1' side chain on structure-activity

  摘要：

  A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T-lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.

  DOI：

  10.1021/jm00088a004

文献信息

• HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: An investigation into the role of the P1' side chain on structure-activity
  作者：Steven D. Young、Linda S. Payne、Wayne J. Thompson、Neil Gaffin、Terry A. Lyle、Susan F. Britcher、Samuel L. Graham、Thomas H. Schultz、Albert A. Deana

  DOI：10.1021/jm00088a004

  日期：1992.5

  A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T-lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.