tert-butyl 4-[(2S)-3-[[(2S,3R)-1-cyclohexyl-4-[(2R)-1-ethoxy-4-methyl-1-oxopentan-2-yl]sulfanyl-3-hydroxybutan-2-yl]amino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-oxopropyl]imidazole-1-carboxylate | 142843-16-1

• 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 4-[(2S)-3-[[(2S,3R)-1-cyclohexyl-4-[(2R)-1-ethoxy-4-methyl-1-oxopentan-2-yl]sulfanyl-3-hydroxybutan-2-yl]amino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-oxopropyl]imidazole-1-carboxylate
• CAS: 142843-16-1；142926-13-4
• 化学式: C₄₃H₆₇N₅O₉S
• 分子量: 830.099
• InChiKey: SWRNANUZPONGSB-CPDVWBMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.36
• 重原子数：
  58.0
• 可旋转键数：
  19.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  187.18
• 氢给体数：
  4.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(2S)-3-[[(2S,3R)-1-cyclohexyl-4-[(2R)-1-ethoxy-4-methyl-1-oxopentan-2-yl]sulfanyl-3-hydroxybutan-2-yl]amino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-oxopropyl]imidazole-1-carboxylate 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以26%的产率得到tert-butyl 4-[(2S)-3-[[(2S,3R)-1-cyclohexyl-4-[(2R)-1-ethoxy-4-methyl-1-oxopentan-2-yl]sulfonyl-3-hydroxybutan-2-yl]amino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-oxopropyl]imidazole-1-carboxylate
  参考文献：
  名称：

  Inhibitors of human renin with C-termini derived from amides and esters of .alpha.-mercaptoalkanoic acids

  摘要：

  New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. The corresponding sulfoxide and sulfone analogues were also investigated. Some of these derivatives, including one with a stable BocPhe replacement, were relatively potent inhibitors of human plasma renin, having IC50 values below 10 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys (Macaca mulatta) at 0.06-1 mg/kg, they reduced plasma renin activity by 87-94%. However, the accompanying drop in blood pressure was of short duration.

  DOI：

  10.1021/jm00093a009
• 作为产物：
  描述：

  ethyl (2R)-2-[(2R,3S)-4-cyclohexyl-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]sulfanyl-4-methylpentanoate 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 tert-butyl 4-[(2S)-3-[[(2S,3R)-1-cyclohexyl-4-[(2R)-1-ethoxy-4-methyl-1-oxopentan-2-yl]sulfanyl-3-hydroxybutan-2-yl]amino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-oxopropyl]imidazole-1-carboxylate
  参考文献：
  名称：

  Inhibitors of human renin with C-termini derived from amides and esters of .alpha.-mercaptoalkanoic acids

  摘要：

  New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. The corresponding sulfoxide and sulfone analogues were also investigated. Some of these derivatives, including one with a stable BocPhe replacement, were relatively potent inhibitors of human plasma renin, having IC50 values below 10 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys (Macaca mulatta) at 0.06-1 mg/kg, they reduced plasma renin activity by 87-94%. However, the accompanying drop in blood pressure was of short duration.

  DOI：

  10.1021/jm00093a009