tert-butyl N-[[(2S,3S)-2-hydroxy-3-[[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutyl]-[(4-phenylphenyl)methyl]amino]carbamate | 191594-68-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl N-[[(2S,3S)-2-hydroxy-3-[[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutyl]-[(4-phenylphenyl)methyl]amino]carbamate
• CAS: 191594-68-0
• 化学式: C₃₅H₄₆N₄O₆
• 分子量: 618.773
• InChiKey: UAORNRHRAOINEK-CHQNGUEUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  45
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[[(2S,3S)-2-hydroxy-3-[[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutyl]-[(4-phenylphenyl)methyl]amino]carbamate 在 N-甲基吗啉 、 盐酸 、 O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 19.25h， 生成 2,5,6,10,13-Pentaazatetradecanedioic acid, 6-((1,1'-biphenyl)-4-ylmethyl)-3-(1,1-dimethylethyl)-8-hydroxy-12-(1-methylethyl)-4,11-dioxo-9-(phenylmethyl)-, dimethyl ester, (3S,8S,9S,12S)-
  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 、 potassium carbonate 、 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， 以 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 26.5h， 生成 tert-butyl N-[[(2S,3S)-2-hydroxy-3-[[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-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

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