(3S)-4-cyclohexyl-2-hydroxy-3-<<(2S)-3-(1H-imidazol-4-yl)-2-<<(2S)-2-(1-oxo-1,3-dihydroisoindol-2-yl)-3-phenylpropionyl>amino>propionyl>amino>butyric acid methyl ester | 137281-94-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3S)-4-cyclohexyl-2-hydroxy-3-<<(2S)-3-(1H-imidazol-4-yl)-2-<<(2S)-2-(1-oxo-1,3-dihydroisoindol-2-yl)-3-phenylpropionyl>amino>propionyl>amino>butyric acid methyl ester
• 英文别名: 4-Cyclohexyl-2-hydroxy-3-{3-(1H-imidazol-4-yl)-2-[2-(1-oxo-1,3-dihydro-isoindol-2-yl)-3-phenyl-propionylamino]-propionylamino}-butyric acid methyl ester；methyl (3S)-4-cyclohexyl-2-hydroxy-3-[[3-(1H-imidazol-5-yl)-2-[[(2S)-2-(3-oxo-1H-isoindol-2-yl)-3-phenylpropanoyl]amino]propanoyl]amino]butanoate
• CAS: 137281-94-8；139236-23-0；139238-62-3
• 化学式: C₃₄H₄₁N₅O₆
• 分子量: 615.729
• InChiKey: VTDMNAHHQZNLDD-SUFZYDOPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  154
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-醛基苯甲酸甲酯 在 1-环已基-2-吗啉乙基碳二亚胺对甲苯磺酸盐 、 sodium cyanoborohydride 、 1-羟基苯并三唑 作用下， 反应 0.25h， 生成 (3S)-4-cyclohexyl-2-hydroxy-3-<<(2S)-3-(1H-imidazol-4-yl)-2-<<(2S)-2-(1-oxo-1,3-dihydroisoindol-2-yl)-3-phenylpropionyl>amino>propionyl>amino>butyric acid methyl ester
  参考文献：
  名称：

  New modified heterocyclic phenylalanine derivatives. Incorporation into potent inhibitors of human renin

  摘要：

  Modified heterocyclic phenylalanine analogues designed as replacements for the P3-P4 region were synthesized and incorporated into renin inhibitors. These inhibitors were found to have significant activity versus human recombinant renin, as well as in vivo activity. The compounds proved to be very resistant to chymotrypsin degradation, as exemplified by compound 8, which remained greater than 60% intact after a 24-h exposure to chymotrypsin. In contrast, the Boc-Phe analogue was nearly completely degraded after 1 h. Compound 6 proved to be the most potent renin inhibitor with an IC50 = 8.9 nM. These stable cyclized phenylalanines should prove to be generally useful as a substitute for Boc-Phe in protease inhibitors.

  DOI：

  10.1021/jm00083a005

文献信息

• New modified heterocyclic phenylalanine derivatives. Incorporation into potent inhibitors of human renin
  作者：Timothy D. Ocain、David D. Deininger、Ralph Russo、Nancie A. Senko、Alan Katz、Jan M. Kitzen、Robert Mitchell、George Oshiro、Anthony Russo

  DOI：10.1021/jm00083a005

  日期：1992.3

  Modified heterocyclic phenylalanine analogues designed as replacements for the P3-P4 region were synthesized and incorporated into renin inhibitors. These inhibitors were found to have significant activity versus human recombinant renin, as well as in vivo activity. The compounds proved to be very resistant to chymotrypsin degradation, as exemplified by compound 8, which remained greater than 60% intact after a 24-h exposure to chymotrypsin. In contrast, the Boc-Phe analogue was nearly completely degraded after 1 h. Compound 6 proved to be the most potent renin inhibitor with an IC50 = 8.9 nM. These stable cyclized phenylalanines should prove to be generally useful as a substitute for Boc-Phe in protease inhibitors.