(RS)-2-amino-3-(5-butyl-3-hydroxyisoxazol-4-yl)propionic acid

• 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: (RS)-2-amino-3-(5-butyl-3-hydroxyisoxazol-4-yl)propionic acid
• 英文别名: 2-Amino-3-(5-butyl-3-oxo-1,2-oxazol-4-yl)propanoic acid
• 化学式: C₁₀H₁₆N₂O₄
• 分子量: 228.248
• InChiKey: BHLLBRLRDRZYJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  Dimethyl 2-acetamido-2-[(5-butyl-3-oxo-1,2-oxazol-4-yl)methyl]propanedioate 以 盐酸 为溶剂， 反应 18.0h， 以45%的产率得到(RS)-2-amino-3-(5-butyl-3-hydroxyisoxazol-4-yl)propionic acid
  参考文献：
  名称：

  Excitatory amino-acid receptor agonists. Synthesis and pharmacology of analogues of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid

  摘要：

  We have previously proposed the existence of a lipophilic cavity of the 2-amino-3-(3-hydroxy-5-methylisoxazol4-yl)propionic acid (AMPA) receptor recognition site capable of accommodating alkyl substituents of limited size in the 5-position of the isoxazole ring. In order to indirectly elucidate the approximate extent of this proposed cavity we have synthesized and pharmacologically characterized a number of AMPA analogues. For most of these AMPA analogues, a positive correlation between AMPA receptor affinity and agonist effect was observed. The only exception was demethyl-AMPA (8a), which showed relatively high AMPA receptor affinity (IC50 = 0.27 mu M) but remarkably weak agonist potency (EC50 = 900 mu M). Whereas the ethyl analogue of AMPA (Et-AMPA) (IC50 = 0.030 mu M; EC50 = 2.3 mu M) has previously been shown to be slightly more potent than AMPA (IC50 = 0.040 mu M; EC50 = 3.5 mu M), substitutions of a propyl or a butyl group for the methyl group of AMPA to give 8b (IC50 = 0.090 mu M; EC50 = 5.0 mu M) or 8f (IC50 = 1.0 mu M; EC50 = 32 mu M), respectively, result in progressive loss of the AMPA agonist effect. Analogues containing larger groups, such as isopentyl (8e), 1-propylbutyl (8g), 2,2-dimethylpropyl (8h), or benzyl (14) groups, were very weak or totally inactive as AMPA receptor ligands.

  DOI：

  10.1016/s0223-5234(97)89085-x

文献信息

• Excitatory amino-acid receptor agonists. Synthesis and pharmacology of analogues of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid
  作者：F.A. Sløk、B Ebert、Y Lang、P Krogsgaard-Larsen、S.M. Lenz、U Madsen

  DOI：10.1016/s0223-5234(97)89085-x

  日期：1997.1

  We have previously proposed the existence of a lipophilic cavity of the 2-amino-3-(3-hydroxy-5-methylisoxazol4-yl)propionic acid (AMPA) receptor recognition site capable of accommodating alkyl substituents of limited size in the 5-position of the isoxazole ring. In order to indirectly elucidate the approximate extent of this proposed cavity we have synthesized and pharmacologically characterized a number of AMPA analogues. For most of these AMPA analogues, a positive correlation between AMPA receptor affinity and agonist effect was observed. The only exception was demethyl-AMPA (8a), which showed relatively high AMPA receptor affinity (IC50 = 0.27 mu M) but remarkably weak agonist potency (EC50 = 900 mu M). Whereas the ethyl analogue of AMPA (Et-AMPA) (IC50 = 0.030 mu M; EC50 = 2.3 mu M) has previously been shown to be slightly more potent than AMPA (IC50 = 0.040 mu M; EC50 = 3.5 mu M), substitutions of a propyl or a butyl group for the methyl group of AMPA to give 8b (IC50 = 0.090 mu M; EC50 = 5.0 mu M) or 8f (IC50 = 1.0 mu M; EC50 = 32 mu M), respectively, result in progressive loss of the AMPA agonist effect. Analogues containing larger groups, such as isopentyl (8e), 1-propylbutyl (8g), 2,2-dimethylpropyl (8h), or benzyl (14) groups, were very weak or totally inactive as AMPA receptor ligands.