methyl (R,S)-2-methoxy-2-(3-methoxy-5-methyl-4-isoxazolyl)acetate | 158327-14-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (R,S)-2-methoxy-2-(3-methoxy-5-methyl-4-isoxazolyl)acetate
• 英文别名: Methyl 2-methoxy-2-(3-methoxy-5-methyl-1,2-oxazol-4-yl)acetate
• CAS: 158327-14-1
• 化学式: C₉H₁₃NO₅
• 分子量: 215.206
• InChiKey: VBATZJQPVHIASS-UHFFFAOYSA-N

物化性质

• 沸点：
  334.1±42.0 °C(predicted)
• 密度：
  1.181±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (R,S)-2-methoxy-2-(3-methoxy-5-methyl-4-isoxazolyl)acetate 在 sodium hydroxide 、 氢溴酸 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 8.5h， 生成 (R,S)-2-methoxy-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid
  参考文献：
  名称：

  Synthesis and Structure-Activity Studies on Acidic Amino Acids and Related Diacids as NMDA Receptor Ligands

  摘要：

  The 3-isoxazolol amino acids (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [(S)-AMPA, 2] and (R,S)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA, 5a) (Figure 1) are potent and specific agonists at the AMPA and N-methyl-D-aspartic acid (NMDA) subtypes, respectively, of(S)-glutamic acid (1) receptors. A number of amino acids and diacids structurally related to AMAA were synthesized and tested electrophysiologically and in receptor-binding assays. The hydroxymethyl analogue 7c of AMAA was an NMDA agonist approximately equipotent with AMAA in the [H-3]CPP-binding assay (IC50 = 7 +/- 3 mu M) and electropharmacologically in the rat cortical wedge model (EC(50) = 8 +/- 2 mu M) In contrast to this, the tert-butyl analogue 7a of AMAA turned out to be an antagonist at NMDA and AMPA receptors. The conformational characteristics of AMAA and 7a c were studied by molecular mechanics calculations. Compound 7a possesses extra steric bulk and shows significant restriction of conformational flexibility compared to AMAA and 7c, which may be determining factors for the observed differences in biological activity. Although the nitrogen atom of quinolinic acid (6) has very weak basic character, 6 is a, perhaps subtype-selective, NMDA receptor agonist and a potent neurotoxic agent. These aspects prompted us to synthesize and test the diacids 8a,b, in which the amino group of AMAA, has been replaced by a methylthio and methoxy group, respectively. Neither compound showed significant affinity for nor depolarizing effects at NMDA receptors. The hydroxymethyl AMPA analogue 3c showed no interaction with NMDA receptors and only weak AMPA agonist effects.

  DOI：

  10.1021/jm00046a009
• 作为产物：
  描述：

  sodium methylate 、 ethyl (R,S)-2-bromo-2-(3-methoxy-4-isoxazolyl)acetate 以 甲醇 为溶剂， 反应 1.0h， 以54%的产率得到methyl (R,S)-2-methoxy-2-(3-methoxy-5-methyl-4-isoxazolyl)acetate
  参考文献：
  名称：

  Synthesis and Structure-Activity Studies on Acidic Amino Acids and Related Diacids as NMDA Receptor Ligands

  摘要：

  The 3-isoxazolol amino acids (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [(S)-AMPA, 2] and (R,S)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA, 5a) (Figure 1) are potent and specific agonists at the AMPA and N-methyl-D-aspartic acid (NMDA) subtypes, respectively, of(S)-glutamic acid (1) receptors. A number of amino acids and diacids structurally related to AMAA were synthesized and tested electrophysiologically and in receptor-binding assays. The hydroxymethyl analogue 7c of AMAA was an NMDA agonist approximately equipotent with AMAA in the [H-3]CPP-binding assay (IC50 = 7 +/- 3 mu M) and electropharmacologically in the rat cortical wedge model (EC(50) = 8 +/- 2 mu M) In contrast to this, the tert-butyl analogue 7a of AMAA turned out to be an antagonist at NMDA and AMPA receptors. The conformational characteristics of AMAA and 7a c were studied by molecular mechanics calculations. Compound 7a possesses extra steric bulk and shows significant restriction of conformational flexibility compared to AMAA and 7c, which may be determining factors for the observed differences in biological activity. Although the nitrogen atom of quinolinic acid (6) has very weak basic character, 6 is a, perhaps subtype-selective, NMDA receptor agonist and a potent neurotoxic agent. These aspects prompted us to synthesize and test the diacids 8a,b, in which the amino group of AMAA, has been replaced by a methylthio and methoxy group, respectively. Neither compound showed significant affinity for nor depolarizing effects at NMDA receptors. The hydroxymethyl AMPA analogue 3c showed no interaction with NMDA receptors and only weak AMPA agonist effects.

  DOI：

  10.1021/jm00046a009