[(R)-3-oxo-4-(3-phenyl-propylamino)-morpholin-2-yl]-acetic acid methyl ester | 609846-48-2

• 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)-3-oxo-4-(3-phenyl-propylamino)-morpholin-2-yl]-acetic acid methyl ester
• 英文别名: methyl 2-[(2R)-3-oxo-4-(3-phenylpropylamino)morpholin-2-yl]acetate
• CAS: 609846-48-2
• 化学式: C₁₆H₂₂N₂O₄
• 分子量: 306.362
• InChiKey: VPAPLPOQHLCAOQ-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(R)-3-oxo-4-(3-phenyl-propylamino)-morpholin-2-yl]-acetic acid methyl ester 在 palladium on activated charcoal lithium hydroxide 、 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 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.67h， 生成 N-(4-Carbamimidoyl-benzyl)-2-[(R)-3-oxo-4-(3-phenyl-propylamino)-morpholin-2-yl]-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：

  D-苹果酸二甲酯 在 palladium on activated charcoal sodium periodate 、 四氧化锇 、 水 、 氢气 、 N-甲基吗啉氧化物 、 silver(l) oxide 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 50.17h， 生成 [(R)-3-oxo-4-(3-phenyl-propylamino)-morpholin-2-yl]-acetic acid methyl ester
  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