tert-butyl N-[[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]-[(4-phenylphenyl)methyl]amino]carbamate | 191594-66-8

• 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: tert-butyl N-[[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]-[(4-phenylphenyl)methyl]amino]carbamate
• CAS: 191594-66-8
• 化学式: C₃₀H₃₄F₃N₃O₄
• 分子量: 557.613
• InChiKey: KOBHKKYSPJAWFX-UIOOFZCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  90.9
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]-[(4-phenylphenyl)methyl]amino]carbamate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以95%的产率得到tert-butyl N-[[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-[(4-phenylphenyl)methyl]amino]carbamate
  参考文献：
  名称：

  New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development

  摘要：

  On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,(8) azadipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) ororthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.

  DOI：

  10.1021/jm970873c
• 作为产物：
  描述：

  对苯基苯甲醛 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 20.0h， 生成 tert-butyl N-[[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]-[(4-phenylphenyl)methyl]amino]carbamate
  参考文献：
  名称：

  New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development

  摘要：

  On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,(8) azadipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) ororthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.

  DOI：

  10.1021/jm970873c

文献信息

• AZAHEXANE DERIVATIVES AS SUBSTRATE ISOSTERS OF RETROVIRAL ASPARATE PROTEASES
  申请人：Novartis AG

  公开号：EP0876336B1

  公开（公告）日：2002-06-05
• US6225345B1
  申请人：——

  公开号：US6225345B1

  公开（公告）日：2001-05-01