3-[(1-benzyloxycarbonylamino-3-methyl-butyl)-hydroxy-phosphinoyl]-2-(3-phenyl-isoxazol-5-ylmethyl)-propionic acid ethyl ester | 1019330-50-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-[(1-benzyloxycarbonylamino-3-methyl-butyl)-hydroxy-phosphinoyl]-2-(3-phenyl-isoxazol-5-ylmethyl)-propionic acid ethyl ester
• 英文别名: [3-ethoxy-3-oxo-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propyl]-[3-methyl-1-(phenylmethoxycarbonylamino)butyl]phosphinic acid
• CAS: 1019330-50-7
• 化学式: C₂₈H₃₅N₂O₇P
• 分子量: 542.569
• InChiKey: AKEKSQOPCCSTOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.63
• 重原子数：
  38.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  127.96
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-[(1-benzyloxycarbonylamino-3-methyl-butyl)-hydroxy-phosphinoyl]-2-(3-phenyl-isoxazol-5-ylmethyl)-propionic acid ethyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以92%的产率得到3-((1-(((benzyloxy)carbonyl)amino)-3-methylbutyl)(hydroxy)phosphoryl)-2-((3-phenylisoxazol-5-yl)methyl)propanoic 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-[(1-benzyloxycarbonylamino-3-methyl-butyl)-hydroxy-phosphinoylmethyl]-pent-4-ynoic acid ethyl ester 、 苯甲醛肟 在 吡啶 、 N-氯代丁二酰亚胺 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 75.0h， 以83%的产率得到3-[(1-benzyloxycarbonylamino-3-methyl-butyl)-hydroxy-phosphinoyl]-2-(3-phenyl-isoxazol-5-ylmethyl)-propionic acid ethyl 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