3-(2-Benzyloxycarbamoyl-3-methyl-butyrylamino)-propionic acid | 847944-79-0

• 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: 3-(2-Benzyloxycarbamoyl-3-methyl-butyrylamino)-propionic acid
• 英文别名: 3-[[3-Methyl-2-(phenylmethoxycarbamoyl)butanoyl]amino]propanoic acid
• CAS: 847944-79-0
• 化学式: C₁₆H₂₂N₂O₅
• 分子量: 322.361
• InChiKey: UOLXERMCFWMMLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-Benzyloxycarbamoyl-3-methyl-butyrylamino)-propionic acid 在 palladium on activated charcoal 氢气 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以91%的产率得到N-[2-[(hydroxyamino)carbonyl]3-methyl-l-oxobutyl]-β-alanine
  参考文献：
  名称：

  Hydroxamic Acids as Potent Inhibitors of Endothelin-Converting Enzyme from Human Bronchiolar Smooth Muscle

  摘要：

  Hydroxamic acids 6a-h, derived from malonyl amino acids, and 25a-d, derived from succinyl amino acids, were synthesized as inhibitors of human bronchiolar smooth muscle endothelin-converting enzyme (HBSM ECE). Several unexpected side reactions were discovered, particularly in the synthesis of hydroxamates derived from succinates. In vitro evaluation against human bronchiolar ECE revealed that in all cases hydroxamates derived from malonate were more potent than hydroxamates derived from succinate. Isopropyl and isobutyl P-1' side chains were suitable; omission of the P-1' Side chain seriously diminished potency. In the P-2' position, several amino acids gave potent malonate-derived hydroxamate inhibitors (6b,d-h, IC50 = 0.2-6.8 nM), and beta-Ala provided an extremely potent inhibitor (6c, IC50 = 0.01 nM). C-terminus carboxylates are much more potent ECE inhibitors than the corresponding amides. Most of the hydroxamates were also potent inhibitors of thermolysin and neutral endopeptidase (NEP); however, the P-2' beta-Ala derivative 6c uniquely inhibited HBSM ECE much more potently than NEP.

  DOI：

  10.1021/jm00012a011
• 作为产物：
  描述：

  2-<<(phenylmethoxy)amino>carbonyl>-3-methylbutanoic acid 在 盐酸 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 3-(2-Benzyloxycarbamoyl-3-methyl-butyrylamino)-propionic acid
  参考文献：
  名称：

  Hydroxamic Acids as Potent Inhibitors of Endothelin-Converting Enzyme from Human Bronchiolar Smooth Muscle

  摘要：

  Hydroxamic acids 6a-h, derived from malonyl amino acids, and 25a-d, derived from succinyl amino acids, were synthesized as inhibitors of human bronchiolar smooth muscle endothelin-converting enzyme (HBSM ECE). Several unexpected side reactions were discovered, particularly in the synthesis of hydroxamates derived from succinates. In vitro evaluation against human bronchiolar ECE revealed that in all cases hydroxamates derived from malonate were more potent than hydroxamates derived from succinate. Isopropyl and isobutyl P-1' side chains were suitable; omission of the P-1' Side chain seriously diminished potency. In the P-2' position, several amino acids gave potent malonate-derived hydroxamate inhibitors (6b,d-h, IC50 = 0.2-6.8 nM), and beta-Ala provided an extremely potent inhibitor (6c, IC50 = 0.01 nM). C-terminus carboxylates are much more potent ECE inhibitors than the corresponding amides. Most of the hydroxamates were also potent inhibitors of thermolysin and neutral endopeptidase (NEP); however, the P-2' beta-Ala derivative 6c uniquely inhibited HBSM ECE much more potently than NEP.

  DOI：

  10.1021/jm00012a011