diethyl N-(N-acetyl-L-isoleucyl-O-benzyl-L-tyrosyl)-1-amino-2-(4-benzyloxyphenyl) ethylphosphonate | 84891-40-7

• 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: diethyl N-(N-acetyl-L-isoleucyl-O-benzyl-L-tyrosyl)-1-amino-2-(4-benzyloxyphenyl) ethylphosphonate
• 英文别名: (2S,3S)-2-acetamido-N-[(2S)-1-[[1-diethoxyphosphoryl-2-(4-phenylmethoxyphenyl)ethyl]amino]-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]-3-methylpentanamide
• CAS: 84891-40-7
• 化学式: C₄₃H₅₄N₃O₈P
• 分子量: 771.891
• InChiKey: UYRYILBVXFVYLQ-LDNWSVRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.37
• 重原子数：
  55.0
• 可旋转键数：
  22.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  141.29
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  diethyl N-(N-acetyl-L-isoleucyl-O-benzyl-L-tyrosyl)-1-amino-2-(4-benzyloxyphenyl) ethylphosphonate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 diethyl N-(N-acetyl-L-isoleucyl-L-tyrosyl)-1-amino-2-(4-hydroxyphenyl) ethylphosphonate 、 diethyl N-(N-acetyl-L-isoleucyl-L-tyrosyl)-1-amino-2-(4-hydroxyphenyl) ethylphosphonate
  参考文献：
  名称：

  Identification of ACE pharmacophore in the phosphonopeptide metabolite K-26

  摘要：

  The naturally occurring phosphonotripeptide K-26 is a potent angiotensin converting enzyme (ACE) inhibitor containing an alpha-amino phosphonic acid analogue of tyrosine. Previous studies have demonstrated that canonical peptide analogues of K-26 are micromolar inhibitors of ACE. To ascertain the structure-activity relationships in this class of ACE inhibitory natural products, K-26 and eight analogues were chemically synthesized and evaluated. Phosphonyl substitution was found to be the critical determinant of activity, resulting in a 1500-fold increase in ACE inhibition versus carboxyl analogues. Secondarily, the absolute configuration of the terminal alpha-amino phosphonate and N-acetylation were found to significantly modulate ACE inhibitory activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.130
• 作为产物：
  描述：

  diethyl 1-amino-2-(4-benzyloxyphenyl)ethyl phosphonate 、 N-acetyl-L-isoleucyl-O-benzyl-L-tyrosine 在 2,4,6-三甲基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以68%的产率得到diethyl N-(N-acetyl-L-isoleucyl-O-benzyl-L-tyrosyl)-1-amino-2-(4-benzyloxyphenyl) ethylphosphonate
  参考文献：
  名称：

  Identification of ACE pharmacophore in the phosphonopeptide metabolite K-26

  摘要：

  The naturally occurring phosphonotripeptide K-26 is a potent angiotensin converting enzyme (ACE) inhibitor containing an alpha-amino phosphonic acid analogue of tyrosine. Previous studies have demonstrated that canonical peptide analogues of K-26 are micromolar inhibitors of ACE. To ascertain the structure-activity relationships in this class of ACE inhibitory natural products, K-26 and eight analogues were chemically synthesized and evaluated. Phosphonyl substitution was found to be the critical determinant of activity, resulting in a 1500-fold increase in ACE inhibition versus carboxyl analogues. Secondarily, the absolute configuration of the terminal alpha-amino phosphonate and N-acetylation were found to significantly modulate ACE inhibitory activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.130