N'-((2S,3S)-3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-N'-(4-fluoro-benzyl)-hydrazinecarboxylic acid tert-butyl ester | 149267-85-6

• 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)-3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-N'-(4-fluoro-benzyl)-hydrazinecarboxylic acid tert-butyl ester
• 英文别名: tert-butyl N-[(4-fluorophenyl)methyl-[(2S,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutyl]amino]carbamate
• CAS: 149267-85-6
• 化学式: C₂₇H₃₈FN₃O₅
• 分子量: 503.614
• InChiKey: NIYDPHCNFYKFAT-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N'-((2S,3S)-3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-N'-(4-fluoro-benzyl)-hydrazinecarboxylic acid tert-butyl ester 在 1,4-二氧六环 、 N-甲基吗啉 、 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑一水物 作用下， 反应 6.25h， 生成 ((S)-1-{(1S,2S)-1-Benzyl-3-[N-(4-fluoro-benzyl)-N'-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-hydrazino]-2-hydroxy-propylcarbamoyl}-2-methyl-propyl)-carbamic acid methyl 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：

  肼基甲酸叔丁酯 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 19.5h， 生成 N'-((2S,3S)-3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-N'-(4-fluoro-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.