ethyl 2-formylaminobutanoate | 15937-89-0

• 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: ethyl 2-formylaminobutanoate
• 英文别名: 2-formylamino-butyric acid ethyl ester；Ethyl 2-formamidobutanoate；ethyl 2-formamidobutanoate
• CAS: 15937-89-0
• 化学式: C₇H₁₃NO₃
• 分子量: 159.185
• InChiKey: FCQVXXCXTBXTIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-formylaminobutanoate 在 四磷十氧化物 、 magnesium oxide 作用下， 以 氯仿 为溶剂， 反应 20.5h， 生成 2-ethyl-3-hydroxy-4-pyridinecarboxylic acid
  参考文献：
  名称：

  Peroxisome proliferator-activated receptor-γ mediates the anti-inflammatory effect of 3-hydroxy-4-pyridinecarboxylic acid derivatives: Synthesis and biological evaluation

  摘要：

  Seven 3-hydroxy-4-pyridinecarboxylic acid derivatives (HPs), aza-analogues of salicylic acid and structurally close to other potent inflammatory pyridine compounds such as aminopyridinylmethanols and aminopyridinamines, were synthesized, and their anti-inflammatory activity was evaluated. The synthesis was performed by adopting a general procedure involving an intramolecular Diels-Alder cycloaddition of oxazoles with acrylic acid to form various substituted pyridinic acids. The newly synthesized HPs did not exhibit cytotoxic activity on human monocytes-derived macrophages at concentrations up to 10(2) mu M. Anti-inflammatory activity of the compounds was screened in vitro by evaluating the capability to inhibit cytokines release from lipopolysaccharide (LPS) stimulated human macrophages. 3-Hydroxy-1-methyl-4-pyridinecarboxylic acid (24) was found to be the most active HP. At 10 mu M concentration, HP 24 reduced LPS-induced and nuclear factor-kappa B activation and cyclooxygenase-2 expression, while increased intracellular reactive oxygen species generation and peroxisome proliferator-activated receptor (PPAR-gamma) mRNA transcript level. Indeed, pre-treatment of LPS-exposed human macrophages with PPAR-gamma specific antagonist completely prevented HP 24-induced TNF-alpha and IL8 down regulation, demonstrating that the PPAR gamma pathway is mandatory for the HP 24 anti-inflammatory effect. Finally, daily treatment with HP 24 ameliorated the outcome of DSS-induced colitis in mice, significantly reducing colonic MPO activity and IL-1 beta tissue levels. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.024
• 作为产物：
  描述：

  ethyl 2-aminobutyrate 、 原甲酸三乙酯 反应 1.5h， 以85%的产率得到ethyl 2-formylaminobutanoate
  参考文献：
  名称：

  Peroxisome proliferator-activated receptor-γ mediates the anti-inflammatory effect of 3-hydroxy-4-pyridinecarboxylic acid derivatives: Synthesis and biological evaluation

  摘要：

  Seven 3-hydroxy-4-pyridinecarboxylic acid derivatives (HPs), aza-analogues of salicylic acid and structurally close to other potent inflammatory pyridine compounds such as aminopyridinylmethanols and aminopyridinamines, were synthesized, and their anti-inflammatory activity was evaluated. The synthesis was performed by adopting a general procedure involving an intramolecular Diels-Alder cycloaddition of oxazoles with acrylic acid to form various substituted pyridinic acids. The newly synthesized HPs did not exhibit cytotoxic activity on human monocytes-derived macrophages at concentrations up to 10(2) mu M. Anti-inflammatory activity of the compounds was screened in vitro by evaluating the capability to inhibit cytokines release from lipopolysaccharide (LPS) stimulated human macrophages. 3-Hydroxy-1-methyl-4-pyridinecarboxylic acid (24) was found to be the most active HP. At 10 mu M concentration, HP 24 reduced LPS-induced and nuclear factor-kappa B activation and cyclooxygenase-2 expression, while increased intracellular reactive oxygen species generation and peroxisome proliferator-activated receptor (PPAR-gamma) mRNA transcript level. Indeed, pre-treatment of LPS-exposed human macrophages with PPAR-gamma specific antagonist completely prevented HP 24-induced TNF-alpha and IL8 down regulation, demonstrating that the PPAR gamma pathway is mandatory for the HP 24 anti-inflammatory effect. Finally, daily treatment with HP 24 ameliorated the outcome of DSS-induced colitis in mice, significantly reducing colonic MPO activity and IL-1 beta tissue levels. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.024

文献信息

• Vitamin B₂ Analogs. Synthesis and Biological Activity of Homologs of Pyridoxal 5′-Phosphate
  作者：Peter F. Muhlradt、Y. Morino、Esmond E. Snell

  DOI：10.1021/jm00315a012

  日期：1967.5
• Peroxisome proliferator-activated receptor-γ mediates the anti-inflammatory effect of 3-hydroxy-4-pyridinecarboxylic acid derivatives: Synthesis and biological evaluation
  作者：Paola Brun、Annalisa Dean、Valerio Di Marco、Pathak Surajit、Ignazio Castagliuolo、Davide Carta、Maria Grazia Ferlin

  DOI：10.1016/j.ejmech.2013.01.024

  日期：2013.4

  Seven 3-hydroxy-4-pyridinecarboxylic acid derivatives (HPs), aza-analogues of salicylic acid and structurally close to other potent inflammatory pyridine compounds such as aminopyridinylmethanols and aminopyridinamines, were synthesized, and their anti-inflammatory activity was evaluated. The synthesis was performed by adopting a general procedure involving an intramolecular Diels-Alder cycloaddition of oxazoles with acrylic acid to form various substituted pyridinic acids. The newly synthesized HPs did not exhibit cytotoxic activity on human monocytes-derived macrophages at concentrations up to 10(2) mu M. Anti-inflammatory activity of the compounds was screened in vitro by evaluating the capability to inhibit cytokines release from lipopolysaccharide (LPS) stimulated human macrophages. 3-Hydroxy-1-methyl-4-pyridinecarboxylic acid (24) was found to be the most active HP. At 10 mu M concentration, HP 24 reduced LPS-induced and nuclear factor-kappa B activation and cyclooxygenase-2 expression, while increased intracellular reactive oxygen species generation and peroxisome proliferator-activated receptor (PPAR-gamma) mRNA transcript level. Indeed, pre-treatment of LPS-exposed human macrophages with PPAR-gamma specific antagonist completely prevented HP 24-induced TNF-alpha and IL8 down regulation, demonstrating that the PPAR gamma pathway is mandatory for the HP 24 anti-inflammatory effect. Finally, daily treatment with HP 24 ameliorated the outcome of DSS-induced colitis in mice, significantly reducing colonic MPO activity and IL-1 beta tissue levels. (C) 2013 Elsevier Masson SAS. All rights reserved.