N'-[(2S,3S)-2-Hydroxy-4-phenyl-3-(2,2,2-trifluoro-acetylamino)-butyl]-N'-(4-methoxy-benzyl)-hydrazinecarboxylic acid tert-butyl ester | 161852-67-1

• 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'-[(2S,3S)-2-Hydroxy-4-phenyl-3-(2,2,2-trifluoro-acetylamino)-butyl]-N'-(4-methoxy-benzyl)-hydrazinecarboxylic acid tert-butyl ester
• 英文别名: tert-butyl N-[[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]-[(4-methoxyphenyl)methyl]amino]carbamate
• CAS: 161852-67-1
• 化学式: C₂₅H₃₂F₃N₃O₅
• 分子量: 511.541
• InChiKey: FUIQPEPVNGJSEY-SFTDATJTSA-N

物化性质

• 密度：
  1.240±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N'-[(2S,3S)-2-Hydroxy-4-phenyl-3-(2,2,2-trifluoro-acetylamino)-butyl]-N'-(4-methoxy-benzyl)-hydrazinecarboxylic acid tert-butyl ester 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以87%的产率得到N'-((2S,3S)-3-Amino-2-hydroxy-4-phenyl-butyl)-N'-(4-methoxy-benzyl)-hydrazinecarboxylic acid tert-butyl ester
  参考文献：
  名称：

  Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability

  摘要：

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.

  DOI：

  10.1021/jm960022p
• 作为产物：
  描述：

  tert-butyl (E)-2-(4-methoxybenzylidene)hydrazine-1-carboxylate 在 sodium cyanoborohydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 20.0h， 生成 N'-[(2S,3S)-2-Hydroxy-4-phenyl-3-(2,2,2-trifluoro-acetylamino)-butyl]-N'-(4-methoxy-benzyl)-hydrazinecarboxylic acid tert-butyl ester
  参考文献：
  名称：

  Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability

  摘要：

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.

  DOI：

  10.1021/jm960022p

文献信息

• Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability
  作者：Alexander Fässler、Guido Bold、Hans-Georg Capraro、Robert Cozens、Jürgen Mestan、Bernard Poncioni、Johannes Rösel、Marina Tintelnot-Blomley、Marc Lang

  DOI：10.1021/jm960022p

  日期：1996.1.1

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.