{(R)-4-[bis-(3-phenyl-propyl)-amino]-3-oxo-morpholin-2-yl}-acetic acid | 609846-73-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: {(R)-4-[bis-(3-phenyl-propyl)-amino]-3-oxo-morpholin-2-yl}-acetic acid
• 英文别名: 2-[(2R)-4-[bis(3-phenylpropyl)amino]-3-oxomorpholin-2-yl]acetic acid
• CAS: 609846-73-3
• 化学式: C₂₄H₃₀N₂O₄
• 分子量: 410.513
• InChiKey: MLQBUQJIJZROOD-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {(R)-4-[bis-(3-phenyl-propyl)-amino]-3-oxo-morpholin-2-yl}-acetic acid 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.67h， 生成 2-{(R)-4-[Bis-(3-phenyl-propyl)-amino]-3-oxo-morpholin-2-yl}-N-(4-carbamimidoyl-benzyl)-acetamide
  参考文献：
  名称：

  Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold:  Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex

  摘要：

  A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to Mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of alpha-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 muM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with alpha-thrombin is discussed.

  DOI：

  10.1021/jm0307990
• 作为产物：
  描述：

  (R)-2-(2-oxo-ethoxy)-succinic acid dimethyl ester 在 palladium on activated charcoal lithium hydroxide 、 水 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 50.17h， 生成 {(R)-4-[bis-(3-phenyl-propyl)-amino]-3-oxo-morpholin-2-yl}-acetic acid
  参考文献：
  名称：

  Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold:  Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex

  摘要：

  A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to Mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of alpha-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 muM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with alpha-thrombin is discussed.

  DOI：

  10.1021/jm0307990

文献信息

• Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold:  Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex
  作者：Jonas W. Nilsson、Ingemar Kvarnström、Djordje Musil、Ingemar Nilsson、Bertil Samulesson

  DOI：10.1021/jm0307990

  日期：2003.9.1

  A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to Mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of alpha-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 muM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with alpha-thrombin is discussed.