ethyl (2R)-2-[(2R,3S)-4-cyclohexyl-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]sulfanyl-4-methylpentanoate | 142843-08-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (2R)-2-[(2R,3S)-4-cyclohexyl-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]sulfanyl-4-methylpentanoate
• CAS: 142843-08-1
• 化学式: C₂₃H₄₃NO₅S
• 分子量: 445.664
• InChiKey: APHDSPFTUAIGGP-SLFFLAALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.92
• 重原子数：
  30.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  84.86
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  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 、 肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 2-{3-[2-(2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-3-(1H-imidazol-4-yl)-propionylamino]-4-cyclohexyl-2-hydroxy-butylsulfanyl}-4-methyl-pentanoic acid ethyl ester; hydrate
  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：

  (R)-2-mercapto-4-methylpentanoic acid 在 对甲苯磺酸 、 三乙胺 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 4.0h， 生成 ethyl (2R)-2-[(2R,3S)-4-cyclohexyl-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]sulfanyl-4-methylpentanoate
  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