4S-(4-methylubelliferone)-3R-methylazetidin-2-one-1-carboxylic acid (4-methylpyridyl) amide | 226727-16-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4S-(4-methylubelliferone)-3R-methylazetidin-2-one-1-carboxylic acid (4-methylpyridyl) amide
• 英文别名: (2S,3S)-3-methyl-2-(4-methyl-2-oxochromen-7-yl)oxy-4-oxo-N-(pyridin-4-ylmethyl)azetidine-1-carboxamide
• CAS: 226727-16-8
• 化学式: C₂₁H₁₉N₃O₅
• 分子量: 393.399
• InChiKey: VHHGMBXVQJBALM-XCLFUZPHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  97.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4S-(4-methylubelliferone)-3R-methylazetidin-2-one-1-carboxylic acid (4-methylpyridyl) amide 在 乙二胺四乙酸 、 HCl buffer 、 三(2-羰基乙基)磷盐酸盐 、 sodium sulfate 、 三羟甲基氨基甲烷 、 sodium chloride 作用下， 以 二甲基亚砜 为溶剂， 生成 羟甲香豆素
  参考文献：
  名称：

  Inhibition of Human Cytomegalovirus Protease by Monocyclic β-Lactam Derivatives:  Kinetic Characterization Using a Fluorescent Probe

  摘要：

  Recent reports have demonstrated the potential of monocyclic beta-lactam derivatives as inhibitors of human cytomegalovirus (HCMV) protease. Investigation of the mechanism of inhibition by NMR and mass spectrometry has revealed the presence of an acylenzyme intermediate suggesting that beta-lactams are hydrolyzed by the enzyme and cause inhibition by competing with substrate. The potential of a fluorogenic beta-lactam derivative for convenient kinetic characterization of this mechanism has been evaluated using 4S-(4methylumbelliferone)-3R-methylazetidin-2-one-1-carboxylic acid (4-methylpyridyl) amide (1). Upon acylation of the enzyme, the fluorescent umbelliferone moiety is released, allowing for continuous monitoring of the hydrolytic process. Examination of a series of progress curves by numerical analysis has provided valuable information on acylation and deacylation rates which relate to the IC50 values observed for beta-lactams. More importantly the potential of compound 1 as an active site titrating agent for HCMV protease has been exploited, and a simple protocol for rapid determination of active enzyme is described. The data are consistent with the HCMV protease dimer being composed of two functional active sites. This titrating agent represents an important tool that should significantly facilitate the characterization of this novel enzyme.

  DOI：

  10.1021/ja983905+
• 作为产物：
  描述：

  羟甲香豆素 在 sodium hydroxide 、 三丁基膦 、 三乙胺 作用下， 以 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 44.5h， 生成 4S-(4-methylubelliferone)-3R-methylazetidin-2-one-1-carboxylic acid (4-methylpyridyl) amide
  参考文献：
  名称：

  Inhibition of Human Cytomegalovirus Protease by Monocyclic β-Lactam Derivatives:  Kinetic Characterization Using a Fluorescent Probe

  摘要：

  Recent reports have demonstrated the potential of monocyclic beta-lactam derivatives as inhibitors of human cytomegalovirus (HCMV) protease. Investigation of the mechanism of inhibition by NMR and mass spectrometry has revealed the presence of an acylenzyme intermediate suggesting that beta-lactams are hydrolyzed by the enzyme and cause inhibition by competing with substrate. The potential of a fluorogenic beta-lactam derivative for convenient kinetic characterization of this mechanism has been evaluated using 4S-(4methylumbelliferone)-3R-methylazetidin-2-one-1-carboxylic acid (4-methylpyridyl) amide (1). Upon acylation of the enzyme, the fluorescent umbelliferone moiety is released, allowing for continuous monitoring of the hydrolytic process. Examination of a series of progress curves by numerical analysis has provided valuable information on acylation and deacylation rates which relate to the IC50 values observed for beta-lactams. More importantly the potential of compound 1 as an active site titrating agent for HCMV protease has been exploited, and a simple protocol for rapid determination of active enzyme is described. The data are consistent with the HCMV protease dimer being composed of two functional active sites. This titrating agent represents an important tool that should significantly facilitate the characterization of this novel enzyme.

  DOI：

  10.1021/ja983905+