[4-(3-nitro-phenylamino)-3-oxo-morpholin-2-yl]-acetic acid methyl ester | 609846-35-7

• 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: [4-(3-nitro-phenylamino)-3-oxo-morpholin-2-yl]-acetic acid methyl ester
• 英文别名: Methyl 2-[4-(3-nitroanilino)-3-oxomorpholin-2-yl]acetate
• CAS: 609846-35-7
• 化学式: C₁₃H₁₅N₃O₆
• 分子量: 309.279
• InChiKey: VEJOPVOJDYSPNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [4-(3-nitro-phenylamino)-3-oxo-morpholin-2-yl]-acetic acid methyl ester 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成 [4-(3-nitro-phenylamino)-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
• 作为产物：
  描述：

  (S)-2-(2-oxo-ethoxy)-succinic acid dimethyl ester 在 palladium on activated charcoal palladium diacetate 、 水 、 氢气 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 44.0h， 生成 [4-(3-nitro-phenylamino)-3-oxo-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