(2S)-2-[(2-benzyl-1-phenylmethoxycarbonylazetidine-2-carbonyl)amino]propanoic acid | 849919-52-4

• 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: (2S)-2-[(2-benzyl-1-phenylmethoxycarbonylazetidine-2-carbonyl)amino]propanoic acid
• CAS: 849919-52-4
• 化学式: C₂₂H₂₄N₂O₅
• 分子量: 396.443
• InChiKey: QGPCINKYBMXWEQ-CISYCMJJSA-N

物化性质

• 沸点：
  642.3±55.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-[(2-benzyl-1-phenylmethoxycarbonylazetidine-2-carbonyl)amino]propanoic acid 、 盐酸甲胺 在 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 生成 (2R,1'S)-2-benzyl-benzyloxycarbonyl-2-[1'-(methylcarbanoyl)ethyl]carbanoylazetidine 、 (2S,1'S)-2-benzyl-1-benzyloxycarbonyl-2-[1'-(methylcarbamoyl)ethyl]carbamoylazetidine
  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
• 作为产物：
  描述：

  (2RS)-2-benzyl-1-benzyloxycarbonyl-2-carboxylazetidine 在 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2S)-2-[(2-benzyl-1-phenylmethoxycarbonylazetidine-2-carbonyl)amino]propanoic 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