(2S)-2-benzyl-4-oxo-1-[[(1S)-1-phenylethyl]carbamoyl]azetidine-2-carboxylic acid

• 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: (2S)-2-benzyl-4-oxo-1-[[(1S)-1-phenylethyl]carbamoyl]azetidine-2-carboxylic acid
• 化学式: C₂₀H₂₀N₂O₄
• 分子量: 352.39
• InChiKey: DWRFNATXFQHHDE-XOBRGWDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-(-)-1-苯乙基异氰酸酯 在 caesium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2S)-2-benzyl-4-oxo-1-[[(1S)-1-phenylethyl]carbamoyl]azetidine-2-carboxylic acid
  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

• Synthesis and anti-HCMV activity of 1-acyl-β-lactams and 1-acylazetidines derived from phenylalanine
  作者：Guillermo Gerona-Navarro、Ma Jesús Pérez de Vega、Ma Teresa Garcı́a-López、Graciela Andrei、Robert Snoeck、Jan Balzarini、Erik De Clercq、Rosario González-Muñiz

  DOI：10.1016/j.bmcl.2004.02.010

  日期：2004.5

  Different Phe-derived 1-acyl-beta-lactams, analogous to a series of 2-azetidinones acting as HCMV serine protease inhibitors, were synthesized. Some of these compounds were modest inhibitors of the HCMV replication. Interestingly, removal of the carbonyl group of the beta-lactam ring, most likely acting as the serine trap, resulted in an azetidine derivative with anti-HCMV activity comparable to that of the reference compound ganciclovir. (C) 2004 Elsevier Ltd. All rights reserved.
• 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.