2-benzyl-N-[(2S)-1-[2-(4-methylphenyl)ethylamino]-1-oxo-4-phenylbutan-2-yl]-N'-phenylmethoxypropanediamide | 1026045-48-6

• 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: 2-benzyl-N-[(2S)-1-[2-(4-methylphenyl)ethylamino]-1-oxo-4-phenylbutan-2-yl]-N'-phenylmethoxypropanediamide
• CAS: 1026045-48-6
• 化学式: C₃₆H₃₉N₃O₄
• 分子量: 577.723
• InChiKey: FPXWBVRMEHWADU-OBOZPERJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  43
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  96.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-benzyl-N-[(2S)-1-[2-(4-methylphenyl)ethylamino]-1-oxo-4-phenylbutan-2-yl]-N'-phenylmethoxypropanediamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 2-benzyl-N-hydroxy-N'-[(2S)-1-[2-(4-methylphenyl)ethylamino]-1-oxo-4-phenylbutan-2-yl]propanediamide
  参考文献：
  名称：

  Design and Synthesis of Malonic Acid-Based Inhibitors of Human Neutrophil Collagenase (MMP8)

  摘要：

  For most of the known synthetic inhibitors of matrix metalloproteinases (MMPs), a substrate-like binding mode was postulated on the basis of X-ray crystallographic structures of MMP/inhibitor complexes. Conversely, the malonic acid-based inhibitor (2R,S)-HONH-CO-CH(i-Bu)-CO-Ala-Gly-NH2 was found to bind in a surprisingly different manner. Using this compound as a new lead structure, the interaction sites with human neutrophil collagenase (MMP8) were optimized with a series of iteratively designed analogues and with the help of X-ray structural analysis of selected inhibitors to finally produce low molecular weight nonpeptidic compounds of 500-1000-fold improved inhibitory potency.

  DOI：

  10.1021/jm9706426
• 作为产物：
  描述：

  2-苄基-3-乙氧基-3-氧代丙酸钾 在 sodium hydroxide 、 sodium methylate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 25.17h， 生成 2-benzyl-N-[(2S)-1-[2-(4-methylphenyl)ethylamino]-1-oxo-4-phenylbutan-2-yl]-N'-phenylmethoxypropanediamide
  参考文献：
  名称：

  Design and Synthesis of Malonic Acid-Based Inhibitors of Human Neutrophil Collagenase (MMP8)

  摘要：

  For most of the known synthetic inhibitors of matrix metalloproteinases (MMPs), a substrate-like binding mode was postulated on the basis of X-ray crystallographic structures of MMP/inhibitor complexes. Conversely, the malonic acid-based inhibitor (2R,S)-HONH-CO-CH(i-Bu)-CO-Ala-Gly-NH2 was found to bind in a surprisingly different manner. Using this compound as a new lead structure, the interaction sites with human neutrophil collagenase (MMP8) were optimized with a series of iteratively designed analogues and with the help of X-ray structural analysis of selected inhibitors to finally produce low molecular weight nonpeptidic compounds of 500-1000-fold improved inhibitory potency.

  DOI：

  10.1021/jm9706426