2-{(2R,3S)-3-[(S)-2-Amino-3-(4-trifluoromethyl-phenylsulfanyl)-propionylamino]-2-hydroxy-4-phenyl-butyl}-N-tert-butyl-benzamide | 172882-83-6

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: 2-{(2R,3S)-3-[(S)-2-Amino-3-(4-trifluoromethyl-phenylsulfanyl)-propionylamino]-2-hydroxy-4-phenyl-butyl}-N-tert-butyl-benzamide
• 英文别名: 2-[(2R,3S)-3-[[(2S)-2-amino-3-[4-(trifluoromethyl)phenyl]sulfanylpropanoyl]amino]-2-hydroxy-4-phenylbutyl]-N-tert-butylbenzamide
• CAS: 172882-83-6
• 化学式: C₃₁H₃₆F₃N₃O₃S
• 分子量: 587.706
• InChiKey: JDWYODHNQBJWPY-KWXIBIRDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  130
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-{(2R,3S)-3-[(S)-2-Amino-3-(4-trifluoromethyl-phenylsulfanyl)-propionylamino]-2-hydroxy-4-phenyl-butyl}-N-tert-butyl-benzamide 在 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (S)-N-(1S,2R)-<3-<2-<<(1,1-dimethylethyl)amino>carbonyl>phenyl>-2-hydroxy-1-(phenylmethyl)propyl>-2-<(methylsulfonyl)amino>-3-<sulfinyl>propanamide
  参考文献：
  名称：

  Potent Human Immunodeficiency Virus Type 1 Protease Inhibitors That Utilize Noncoded d-Amino Acids as P₂/P₃ Ligands

  摘要：

  Noncoded D-amino acids have been designed to replace the quinaldic amide-asparaginyl moiety (P-2/P-3 ligand) found in several potent human immunodeficiency virus (HIV) protease inhibitors such as LY289612. The substituted nitrogen, optimally an N-methanesulfonyl moiety, served as a CH2CONH2 (asparagine side chain mimic), while the amino acid side chain became the backbone and P-3 ligand of these novel inhibitors. Compounds derived from S-aryl-D-cysteine proved to be patent HIV protease inhibitors which also exhibited potent whole cell antiviral activity. Oxidation of the cysteines to the sulfoxide or sulfone oxidation states resulted in significant improvements in potency. For example, the compound derived from N-(methylsulfonyl)-2-S-naphthylcysteine sulfone, 17c, was a 3.5 nM inhibitor of HIV protease which inhibited the spread of virus in MT4 cells with an IC50 = 4.3 nM. Compounds 17c,g,i were found to be orally bioavailable in a rat model.

  DOI：

  10.1021/jm950576c
• 作为产物：
  描述：

  4-(三氟甲基)苯硫酚 在 sodium hydride 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 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 7.17h， 生成 2-{(2R,3S)-3-[(S)-2-Amino-3-(4-trifluoromethyl-phenylsulfanyl)-propionylamino]-2-hydroxy-4-phenyl-butyl}-N-tert-butyl-benzamide
  参考文献：
  名称：

  Potent Human Immunodeficiency Virus Type 1 Protease Inhibitors That Utilize Noncoded d-Amino Acids as P₂/P₃ Ligands

  摘要：

  Noncoded D-amino acids have been designed to replace the quinaldic amide-asparaginyl moiety (P-2/P-3 ligand) found in several potent human immunodeficiency virus (HIV) protease inhibitors such as LY289612. The substituted nitrogen, optimally an N-methanesulfonyl moiety, served as a CH2CONH2 (asparagine side chain mimic), while the amino acid side chain became the backbone and P-3 ligand of these novel inhibitors. Compounds derived from S-aryl-D-cysteine proved to be patent HIV protease inhibitors which also exhibited potent whole cell antiviral activity. Oxidation of the cysteines to the sulfoxide or sulfone oxidation states resulted in significant improvements in potency. For example, the compound derived from N-(methylsulfonyl)-2-S-naphthylcysteine sulfone, 17c, was a 3.5 nM inhibitor of HIV protease which inhibited the spread of virus in MT4 cells with an IC50 = 4.3 nM. Compounds 17c,g,i were found to be orally bioavailable in a rat model.

  DOI：

  10.1021/jm950576c