N-propionyl-L-valyl-L-valine benzyl ester | 228402-82-2

• 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: N-propionyl-L-valyl-L-valine benzyl ester
• 英文别名: benzyl (2S)-3-methyl-2-[[(2S)-3-methyl-2-(propanoylamino)butanoyl]amino]butanoate
• CAS: 228402-82-2
• 化学式: C₂₀H₃₀N₂O₄
• 分子量: 362.469
• InChiKey: JQOZUTSCSRFYCW-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-propionyl-L-valyl-L-valine benzyl ester 在 palladium on activated charcoal 氢气 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 (S)-N-((S)-2-Hydroxy-1-isobutyl-octyl)-3-methyl-2-((S)-3-methyl-2-propionylamino-butyrylamino)-butyramide
  参考文献：
  名称：

  Simplified Pepstatins:  Synthesis and Evaluation of N-Terminally Modified Analogues

  摘要：

  The promising strategy of gastric ulcer healing with perorally administered epidermal growth factor (EGF) is so far strongly limited by the pepsinic degradation of this therapeutic polypeptide in the stomach. The incorporation of EGF in a bioadhesive polymer-pepsin inhibitor conjugate used as drug carrier matrix, however, might provide sufficient protection toward pepsinic degradation. The synthesis of appropriate pepsin inhibitors represents a prerequisite for the development of such polymer-inhibitor conjugates. The presented study demonstrates that modifications at the N-terminus of simplified analogues of pepstatin which can be synthesized in a simple and straight way result only in slight variations of the inhibitory activity. These analogues display only 10-fold reduced-inhibitory activity, compared to pepstatin A, when bearing a greater N-terminal group like isovaleryl, Boc, or Cbz. Compounds which are substituted at the N-terminus by a shorter N-acyl group like propionyl or cyclopropylcarbonyl show further reduced activity (0.01, compared to pepstatin A). The presence of an amide or a urethane moiety at the N-terminus has no considerable effect on enzyme inhibition. Therefore, the N-terminus of these analogues is able to be modified forming a covalent bond to various bioadhesive polymers via a suitable functionality.

  DOI：

  10.1021/jm9807306
• 作为产物：
  描述：

  N-propionyl-L-valine 、 L-缬氨酸苄酯 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 以79%的产率得到N-propionyl-L-valyl-L-valine benzyl ester
  参考文献：
  名称：

  Simplified Pepstatins:  Synthesis and Evaluation of N-Terminally Modified Analogues

  摘要：

  The promising strategy of gastric ulcer healing with perorally administered epidermal growth factor (EGF) is so far strongly limited by the pepsinic degradation of this therapeutic polypeptide in the stomach. The incorporation of EGF in a bioadhesive polymer-pepsin inhibitor conjugate used as drug carrier matrix, however, might provide sufficient protection toward pepsinic degradation. The synthesis of appropriate pepsin inhibitors represents a prerequisite for the development of such polymer-inhibitor conjugates. The presented study demonstrates that modifications at the N-terminus of simplified analogues of pepstatin which can be synthesized in a simple and straight way result only in slight variations of the inhibitory activity. These analogues display only 10-fold reduced-inhibitory activity, compared to pepstatin A, when bearing a greater N-terminal group like isovaleryl, Boc, or Cbz. Compounds which are substituted at the N-terminus by a shorter N-acyl group like propionyl or cyclopropylcarbonyl show further reduced activity (0.01, compared to pepstatin A). The presence of an amide or a urethane moiety at the N-terminus has no considerable effect on enzyme inhibition. Therefore, the N-terminus of these analogues is able to be modified forming a covalent bond to various bioadhesive polymers via a suitable functionality.

  DOI：

  10.1021/jm9807306

文献信息

• Simplified Pepstatins:  Synthesis and Evaluation of N-Terminally Modified Analogues
  作者：Martin Kratzel、Birgit Schlichtner、Roland Kirchmayer、Andreas Bernkop-Schnürch

  DOI：10.1021/jm9807306

  日期：1999.6.1

  The promising strategy of gastric ulcer healing with perorally administered epidermal growth factor (EGF) is so far strongly limited by the pepsinic degradation of this therapeutic polypeptide in the stomach. The incorporation of EGF in a bioadhesive polymer-pepsin inhibitor conjugate used as drug carrier matrix, however, might provide sufficient protection toward pepsinic degradation. The synthesis of appropriate pepsin inhibitors represents a prerequisite for the development of such polymer-inhibitor conjugates. The presented study demonstrates that modifications at the N-terminus of simplified analogues of pepstatin which can be synthesized in a simple and straight way result only in slight variations of the inhibitory activity. These analogues display only 10-fold reduced-inhibitory activity, compared to pepstatin A, when bearing a greater N-terminal group like isovaleryl, Boc, or Cbz. Compounds which are substituted at the N-terminus by a shorter N-acyl group like propionyl or cyclopropylcarbonyl show further reduced activity (0.01, compared to pepstatin A). The presence of an amide or a urethane moiety at the N-terminus has no considerable effect on enzyme inhibition. Therefore, the N-terminus of these analogues is able to be modified forming a covalent bond to various bioadhesive polymers via a suitable functionality.