4-oxo-4-(phenylmethoxy)butyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-<<(2S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-<<(phenylmethoxy)carbonyl>amino>propanoyl>amino>butanoate | 134848-75-2

• 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: 4-oxo-4-(phenylmethoxy)butyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-<<(2S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-<<(phenylmethoxy)carbonyl>amino>propanoyl>amino>butanoate
• 英文别名: 4-oxo-4-(phenylmethoxy)butyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-[((2S)-2-{[(1,1-dimethylethoxy)carbonyl]amino}-3-{[(phenylmethoxy)carbonyl]amino}propanoyl)amino]butanoate；(4-oxo-4-phenylmethoxybutyl) (2R,3S)-4-cyclohexyl-2-hydroxy-3-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(phenylmethoxycarbonylamino)propanoyl]amino]butanoate
• CAS: 134848-75-2
• 化学式: C₃₇H₅₁N₃O₁₀
• 分子量: 697.826
• InChiKey: QQADJRXKCZTJJB-LHHUKBANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.69
• 重原子数：
  50.0
• 可旋转键数：
  17.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  178.59
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  4-oxo-4-(phenylmethoxy)butyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-<<(2S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-<<(phenylmethoxy)carbonyl>amino>propanoyl>amino>butanoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 (2R,3S)-3-((S)-3-Amino-2-tert-butoxycarbonylamino-propionylamino)-4-cyclohexyl-2-hydroxy-butyric acid 3-carboxy-propyl ester
  参考文献：
  名称：

  Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors

  摘要：

  Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65-mu-M, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle.

  DOI：

  10.1021/jm00113a005
• 作为产物：
  描述：

  4-oxo-4-(phenylmethoxy)butyl (4S,5R)-4-(cyclohexylmethyl)-2,2-dimethyl-3-<(1,1-dimethylethoxy)carbonyl>-5-oxazolidinecarboxylate 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 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 4-oxo-4-(phenylmethoxy)butyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-<<(2S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-<<(phenylmethoxy)carbonyl>amino>propanoyl>amino>butanoate
  参考文献：
  名称：

  Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors

  摘要：

  Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65-mu-M, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle.

  DOI：

  10.1021/jm00113a005