methyl (2S)-2-benzyl-4-oxo-1-[[(1S)-1-phenylethyl]carbamoyl]azetidine-2-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: methyl (2S)-2-benzyl-4-oxo-1-[[(1S)-1-phenylethyl]carbamoyl]azetidine-2-carboxylate
• 化学式: C₂₁H₂₂N₂O₄
• 分子量: 366.417
• InChiKey: BJHWMKKBQRZXLG-BTYIYWSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-(-)-1-苯乙基异氰酸酯 、 4-benzyl-4-methoxycarbonyl-2-azetidinone 在 caesium carbonate 作用下， 以 四氢呋喃 为溶剂， 以62%的产率得到methyl (2S)-2-benzyl-4-oxo-1-[[(1S)-1-phenylethyl]carbamoyl]azetidine-2-carboxylate
  参考文献：
  名称：

  From 1-Acyl-β-lactam Human Cytomegalovirus Protease Inhibitors to 1-Benzyloxycarbonylazetidines with Improved Antiviral Activity. A Straightforward Approach To Convert Covalent to Noncovalent Inhibitors

  摘要：

  Starting from the structure of known beta-lactam covalent human cytomegalovirus (HCMV) protease inhibitors and from the knowledge of the residues implicated in the active site of this enzyme, we designed a series of phenylalanine-derived 2-azetidinones bearing a 4-carboxylate moiety that could be apt for additional interactions with the guanidine group of the Arg165/ Arg166 residues of the viral protease. Some compounds within this series showed anti-HCMV activity at 10-50 mu M, but rather high toxicity. The presence of aromatic 1-acyl groups and a certain hydrophobic character in the region of the 4-carboxylate were stringent requirements for anti-HCMV activity. To go a step ahead into the search for effective HCMV medicines, we then envisaged a series of noncovalent inhibitors by simple deletion of the carbonyl group in the beta-lactam derivatives to provide the corresponding azetidines. This led to low micromolar inhibitors of HCMV replication, with 17 and 27 being particularly promising lead compounds for further investigation, although their toxicity still needs to be lowered.

  DOI：

  10.1021/jm0492812

文献信息

• From 1-Acyl-β-lactam Human Cytomegalovirus Protease Inhibitors to 1-Benzyloxycarbonylazetidines with Improved Antiviral Activity. A Straightforward Approach To Convert Covalent to Noncovalent Inhibitors
  作者：Guillermo Gerona-Navarro、M. Jesús Pérez de Vega、M. Teresa García-López、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini、Rosario González-Muñiz

  DOI：10.1021/jm0492812

  日期：2005.4.1

  Starting from the structure of known beta-lactam covalent human cytomegalovirus (HCMV) protease inhibitors and from the knowledge of the residues implicated in the active site of this enzyme, we designed a series of phenylalanine-derived 2-azetidinones bearing a 4-carboxylate moiety that could be apt for additional interactions with the guanidine group of the Arg165/ Arg166 residues of the viral protease. Some compounds within this series showed anti-HCMV activity at 10-50 mu M, but rather high toxicity. The presence of aromatic 1-acyl groups and a certain hydrophobic character in the region of the 4-carboxylate were stringent requirements for anti-HCMV activity. To go a step ahead into the search for effective HCMV medicines, we then envisaged a series of noncovalent inhibitors by simple deletion of the carbonyl group in the beta-lactam derivatives to provide the corresponding azetidines. This led to low micromolar inhibitors of HCMV replication, with 17 and 27 being particularly promising lead compounds for further investigation, although their toxicity still needs to be lowered.