(2R,4S,5S)-5-tert-Butoxycarbonylamino-4-(tert-butyl-dimethyl-silanyloxy)-6-phenyl-2-(4-trifluoromethyl-benzyl)-hexanoic acid | 158654-80-9

• 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)-5-tert-Butoxycarbonylamino-4-(tert-butyl-dimethyl-silanyloxy)-6-phenyl-2-(4-trifluoromethyl-benzyl)-hexanoic acid
• 英文别名: (2R,4S,5S)-4-[tert-butyl(dimethyl)silyl]oxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenyl-2-[[4-(trifluoromethyl)phenyl]methyl]hexanoic acid
• CAS: 158654-80-9
• 化学式: C₃₁H₄₄F₃NO₅Si
• 分子量: 595.775
• InChiKey: MMDQHCKGIXOVDF-AFESJLNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.87
• 重原子数：
  41
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,4S,5S)-5-tert-Butoxycarbonylamino-4-(tert-butyl-dimethyl-silanyloxy)-6-phenyl-2-(4-trifluoromethyl-benzyl)-hexanoic acid 在 四丁基氟化铵 、 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 [(1S,2S,4R)-1-Benzyl-2-hydroxy-4-((1S,2R)-2-hydroxy-indan-1-ylcarbamoyl)-5-(4-trifluoromethyl-phenyl)-pentyl]-carbamic acid tert-butyl ester
  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：

  (5S,1'S)-carbetoxy-5-<1-<<(1',1-dimethylothoxy)carbonyl>amino>-2-phenylmethyl>dihydrofuran-2(3H)-one 在 咪唑 、 lithium hydroxide 、 sodium ethanolate 作用下， 以 乙二醇二甲醚 、 乙醇 、 甲苯 为溶剂， 反应 78.0h， 生成 (2R,4S,5S)-5-tert-Butoxycarbonylamino-4-(tert-butyl-dimethyl-silanyloxy)-6-phenyl-2-(4-trifluoromethyl-benzyl)-hexanoic acid
  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.