tert-butyl N-[(2S)-1-[methoxy(methyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]carbamate | 300351-89-7

• 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: tert-butyl N-[(2S)-1-[methoxy(methyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]carbamate
• CAS: 300351-89-7
• 化学式: C₂₂H₂₈N₂O₄
• 分子量: 384.475
• InChiKey: YZAYPNXSEUDACV-IBGZPJMESA-N

物化性质

• 密度：
  1.120±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  67.87
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-1-[methoxy(methyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]carbamate 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 氢气 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 27.33h， 生成 ethyl (4R)-4-amino-2-methyl-5-(4-phenylphenyl)pentanoate
  参考文献：
  名称：

  Dicarboxylic Acid Dipeptide Neutral Endopeptidase Inhibitors

  摘要：

  The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described. In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo. Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys. Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment. A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements. Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a. Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.

  DOI：

  10.1021/jm00010a014
• 作为产物：
  描述：

  n-叔丁氧基羰基-3-(4-联苯)-2-氨基丙酸-(S)-甲酯 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 tert-butyl N-[(2S)-1-[methoxy(methyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]carbamate
  参考文献：
  名称：

  Dicarboxylic Acid Dipeptide Neutral Endopeptidase Inhibitors

  摘要：

  The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described. In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo. Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys. Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment. A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements. Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a. Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.

  DOI：

  10.1021/jm00010a014