1-(4-biphenylyl)-5(S)-2,5-diamino-4(S)-hydroxy-6-phenyl-2-azahexane hydrochloride | 478547-15-8

• 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: 1-(4-biphenylyl)-5(S)-2,5-diamino-4(S)-hydroxy-6-phenyl-2-azahexane hydrochloride
• 英文别名: 1-(4-biphenylyl)-4(S)-hydroxy-5(S)-2,5-diamino-6-phenyl-2-azahexane hydrochloride；(2S,3S)-3-amino-1-[amino-[(4-phenylphenyl)methyl]amino]-4-phenylbutan-2-ol;hydrochloride
• CAS: 478547-15-8
• 化学式: C₂₃H₂₇N₃O*ClH
• 分子量: 397.948
• InChiKey: LHEQFXPPAWBUQK-SJEIDVEUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  28.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  75.51
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  MOC-L-缬氨酸 、 1-(4-biphenylyl)-5(S)-2,5-diamino-4(S)-hydroxy-6-phenyl-2-azahexane hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 生成 1-[2(S)-Hydroxy-3(S)-(N-methoxycarbonyl-(L)-valyl)amino-4-phenylbutyl]-1-[4-biphenylylmethyl]-2-[N-methoxycarbonyl-(L)-valyl]-hydrazine
  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 盐酸 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 23.0h， 生成 1-(4-biphenylyl)-5(S)-2,5-diamino-4(S)-hydroxy-6-phenyl-2-azahexane hydrochloride
  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