1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-5(S)-2,5-bis-[N-(N-methoxycarbonyl-(L)-tert-leucyl)-amino]-6-phenyl-2-azahexane | 198903-88-7

• 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: 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-5(S)-2,5-bis-[N-(N-methoxycarbonyl-(L)-tert-leucyl)-amino]-6-phenyl-2-azahexane
• 英文别名: methyl N-[(1S)-1-[[(1S,2S)-1-benzyl-2-hydroxy-3-[[[(2S)-2-(methoxycarbonylamino)-3,3-dimethyl-butanoyl]amino]-[(4-thiazol-5-ylphenyl)methyl]amino]propyl]carbamoyl]-2,2-dimethyl-propyl]carbamate；methyl N-[(2S)-1-[2-[(2S,3S)-2-hydroxy-3-[[(2S)-2-(methoxycarbonylamino)-3,3-dimethylbutanoyl]amino]-4-phenylbutyl]-2-[[4-(1,3-thiazol-5-yl)phenyl]methyl]hydrazinyl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
• CAS: 198903-88-7
• 化学式: C₃₆H₅₀N₆O₇S
• 分子量: 710.895
• InChiKey: QUDILHMWVMUYMR-BPYIEZMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  50
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  200
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N-甲氧羰基-L-叔亮氨酸 在 N-甲基吗啉 、 甲酸 、 1-羟基苯并三唑 、 O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 反应 25.75h， 生成 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-5(S)-2,5-bis-[N-(N-methoxycarbonyl-(L)-tert-leucyl)-amino]-6-phenyl-2-azahexane
  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