{(1S,2R)-3-[((2R,3S)-3-Amino-2-hydroxy-4-phenyl-butyl)-(9H-fluoren-9-ylmethoxycarbonyl)-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid tert-butyl ester | 162538-99-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: {(1S,2R)-3-[((2R,3S)-3-Amino-2-hydroxy-4-phenyl-butyl)-(9H-fluoren-9-ylmethoxycarbonyl)-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid tert-butyl ester
• CAS: 162538-99-0
• 化学式: C₄₀H₄₇N₃O₆
• 分子量: 665.83
• InChiKey: OVSUYVACPPWCDL-DNMDQSTESA-N

物化性质

• 沸点：
  847.801±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.221±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.67
• 重原子数：
  49.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  134.35
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  {(1S,2R)-3-[((2R,3S)-3-Amino-2-hydroxy-4-phenyl-butyl)-(9H-fluoren-9-ylmethoxycarbonyl)-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid tert-butyl ester 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 {(1S,2R)-1-Benzyl-3-[(9H-fluoren-9-ylmethoxycarbonyl)-((2R,3S)-2-hydroxy-3-methylamino-4-phenyl-butyl)-amino]-2-hydroxy-propyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

  摘要：

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

  DOI：

  10.1021/jm00038a005
• 作为产物：
  描述：

  {(1S,2R)-1-Benzyl-3-[((2R,3S)-3-benzyloxycarbonylamino-2-hydroxy-4-phenyl-butyl)-(9H-fluoren-9-ylmethoxycarbonyl)-amino]-2-hydroxy-propyl}-carbamic acid tert-butyl ester 在 palladium on activated charcoal 1,4-环己二烯 、 氢气 作用下， 以 乙醇 为溶剂， 反应 3.5h， 以100%的产率得到{(1S,2R)-3-[((2R,3S)-3-Amino-2-hydroxy-4-phenyl-butyl)-(9H-fluoren-9-ylmethoxycarbonyl)-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

  摘要：

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

  DOI：

  10.1021/jm00038a005