2-[(2-Carboxy-3-phenyl-propyl)-hydroxy-phosphinoyl]-pyrrolidine-1-carboxylic acid benzyl ester | 1019330-30-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-[(2-Carboxy-3-phenyl-propyl)-hydroxy-phosphinoyl]-pyrrolidine-1-carboxylic acid benzyl ester
• 英文别名: 2-benzyl-3-[hydroxy-(1-phenylmethoxycarbonylpyrrolidin-2-yl)phosphoryl]propanoic acid
• CAS: 1019330-30-3
• 化学式: C₂₂H₂₆NO₆P
• 分子量: 431.425
• InChiKey: KGHGKJWLKWMFHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[(2-Carboxy-3-phenyl-propyl)-hydroxy-phosphinoyl]-pyrrolidine-1-carboxylic acid benzyl ester 在 氢气 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 以95%的产率得到2-Benzyl-3-(hydroxy-pyrrolidin-2-yl-phosphinoyl)-propionic acid
  参考文献：
  名称：

  Development of Potent and Selective Phosphinic Peptide Inhibitors of Angiotensin-Converting Enzyme 2

  摘要：

  Arimotensin-converting enzyme 2 (ACE2), a recently identified human homologue of angiotensin-converting enzyme, is a zinc metallocarboxypeptidase which may play a unique role in cardiovascular and renal function. Here we report the discovery of potent and selective inhibitors of ACE2, which have been identified by evaluating a series of phosphinic di- and tripeptides of the general formula: Z-Xaa(PO2-CH2)YaaOH and Ac-Zaa-Xaa(PO2-CH2)YaaOH. The most potent inhibitor in this series is a tripeptide that displays a K-i value of 0.4 nM toward ACE2 and is 3 orders of magnitude less potent toward carboxypeptidase A. Phosphinic tripeptides exhibit high potency exclusively when the Xaa position is occupied by a pseudoproline. A model of interaction between one inhibitor of this series and ACE2 suggests that the critical role played by a proline in inhibitors, but also for substrates hydrolysis, may rely on the presence of Tyr(510) in the ACE2 active site.

  DOI：

  10.1021/jm701275z
• 作为产物：
  描述：

  2-[(2-ethoxycarbonyl-3-phenyl-propyl)-hydroxy-phosphinoyl]-pyrrolidine-1-carboxylic acid benzyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以74%的产率得到2-[(2-Carboxy-3-phenyl-propyl)-hydroxy-phosphinoyl]-pyrrolidine-1-carboxylic acid benzyl ester
  参考文献：
  名称：

  Development of Potent and Selective Phosphinic Peptide Inhibitors of Angiotensin-Converting Enzyme 2

  摘要：

  Arimotensin-converting enzyme 2 (ACE2), a recently identified human homologue of angiotensin-converting enzyme, is a zinc metallocarboxypeptidase which may play a unique role in cardiovascular and renal function. Here we report the discovery of potent and selective inhibitors of ACE2, which have been identified by evaluating a series of phosphinic di- and tripeptides of the general formula: Z-Xaa(PO2-CH2)YaaOH and Ac-Zaa-Xaa(PO2-CH2)YaaOH. The most potent inhibitor in this series is a tripeptide that displays a K-i value of 0.4 nM toward ACE2 and is 3 orders of magnitude less potent toward carboxypeptidase A. Phosphinic tripeptides exhibit high potency exclusively when the Xaa position is occupied by a pseudoproline. A model of interaction between one inhibitor of this series and ACE2 suggests that the critical role played by a proline in inhibitors, but also for substrates hydrolysis, may rely on the presence of Tyr(510) in the ACE2 active site.

  DOI：

  10.1021/jm701275z

文献信息

• Development of Potent and Selective Phosphinic Peptide Inhibitors of Angiotensin-Converting Enzyme 2
  作者：Andreas Mores、Magdalini Matziari、Fabrice Beau、Philippe Cuniasse、Athanasios Yiotakis、Vincent Dive

  DOI：10.1021/jm701275z

  日期：2008.4.1

  Arimotensin-converting enzyme 2 (ACE2), a recently identified human homologue of angiotensin-converting enzyme, is a zinc metallocarboxypeptidase which may play a unique role in cardiovascular and renal function. Here we report the discovery of potent and selective inhibitors of ACE2, which have been identified by evaluating a series of phosphinic di- and tripeptides of the general formula: Z-Xaa(PO2-CH2)YaaOH and Ac-Zaa-Xaa(PO2-CH2)YaaOH. The most potent inhibitor in this series is a tripeptide that displays a K-i value of 0.4 nM toward ACE2 and is 3 orders of magnitude less potent toward carboxypeptidase A. Phosphinic tripeptides exhibit high potency exclusively when the Xaa position is occupied by a pseudoproline. A model of interaction between one inhibitor of this series and ACE2 suggests that the critical role played by a proline in inhibitors, but also for substrates hydrolysis, may rely on the presence of Tyr(510) in the ACE2 active site.