(乙酰氨基)[(3-甲氧基-5-甲基-4-异恶唑基)甲基]丙二酸二乙酯 | 75989-23-0

• 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
• 中文名称: (乙酰氨基)[(3-甲氧基-5-甲基-4-异恶唑基)甲基]丙二酸二乙酯
• 英文名称: diethyl acetamido<(3-methoxy-5-methylisoxazol-4-yl)methyl>malonate
• 英文别名: diethyl 3-methoxy-5-methyl-(1,2-isoxazol-4-yl)methylacetamidomalonate；diethyl acetamido-(3-methoxy-5-methylisoxazol-4-ylmethyl)malonate；(Acetylamino)[(3-methoxy-5-methyl-4-isoxazolyl)methyl]propanedioic Acid Diethyl Ester；diethyl 2-acetamido-2-[(3-methoxy-5-methyl-1,2-oxazol-4-yl)methyl]propanedioate
• CAS: 75989-23-0
• 化学式: C₁₅H₂₂N₂O₇
• 分子量: 342.349
• InChiKey: SYYIWPOFCIVQDV-UHFFFAOYSA-N

物化性质

• 沸点：
  504.6±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (乙酰氨基)[(3-甲氧基-5-甲基-4-异恶唑基)甲基]丙二酸二乙酯 在 氢溴酸 、 三乙胺 作用下， 以 乙醇 、 水 为溶剂， 反应 0.33h， 以86%的产率得到(R,S)-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸
  参考文献：
  名称：

  Hansen; Krogsgaard-Larsen, Journal of the Chemical Society. Perkin transactions I, 1980, vol. 8, p. 1826 - 1833

  摘要：

  DOI：
• 作为产物：
  描述：

  3-甲氧基-5-甲基-1,2-恶唑-4-羧酸 在 氯化亚砜 、 硼烷 、 sodium hydride 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 64.17h， 生成 (乙酰氨基)[(3-甲氧基-5-甲基-4-异恶唑基)甲基]丙二酸二乙酯
  参考文献：
  名称：

  通过3-溴异恶唑中间体方便地合成（±）-2-氨基-3-（3-羟基-5-甲基异恶唑-4-基）丙酸氢溴酸盐

  摘要：

  由克丁酸2-丁酸酯制得的兴奋性氨基酸±2-氨基-3-（3-羟基-5-甲基异恶唑-4-基）丙酸氢溴酸盐的克量为3.3％。关键步骤是轻松制备3-溴-5-甲基异恶唑-4-羧酸甲酯。

  DOI：

  10.1002/jhet.5570340155

文献信息

• Synthesis and Structure-Activity Studies on Excitatory Amino Acids Structurally Related to Ibotenic Acid
  作者：Povl Krogsgaard-Larsen、Lotte Brehm、Jørgen S. Johansen、Peter Vinzents、Jørn Lauridsen、David R. Curtis

  DOI：10.1021/jm50001a023

  日期：1985.5

  The structure of 7-HPCA in the crystalline state was established by X-ray analyses. The preferred conformation of 10 in aqueous solution was determined by 1H NMR spectroscopy. On the basis of these studies, 7-HPCA as well as 10 were shown to adopt preferentially conformations with the carboxylate groups in equatorial positions. It is suggested that AMPA, 7-HPCA, and 10 interact with quisqualic acid receptors

  以卵磷脂为铅，（RS）-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）和（RS）-3-羟基-4,5,6的类似物，合成了7-四氢异恶唑并[5,4-c]吡啶-7-羧酸（7-HPCA），并通过微电泳技术测试了猫脊髓中神经元的兴奋性，并测试了海藻酸的结合抑制剂。像AMPA和7-HPCA，（RS）-3-羟基-4,5,6,7-四氢异恶唑并[5,4-c]-吡啶-5-羧酸（10，5-HPCA）和（RS）- 3-羟基-5-（溴甲基）异恶唑-4-丙酸（11，ABPA）被证明与假定为生理性谷氨酸受体的中央喹喹酸受体有效且选择性地相互作用。7-HPCA或10的类似物，其中一个或两个酸基均被掩盖，它们作为神经元兴奋剂非常弱或无活性，对兴奋性氨基酸受体没有拮抗作用。通过X射线分析确定了处于结晶状态的7-HPCA的结构。通过1 H NMR光谱确定水溶液中10的优选构象。在这些研究的基础上，显示7-HPCA以及
• Enzymic resolution and binding to rat brain membranes of the glutamic acid agonist .alpha.-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
  作者：Jan J. Hansen、Joern Lauridsen、Elsebet Nielsen、Povl Krogsgaard-Larsen

  DOI：10.1021/jm00360a021

  日期：1983.6

  The enantiomers of the glutamic acid central nervous system receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were prepared via kinetic resolution of the racemic N-acetylated 3-methoxy derivative by reusable, immobilized aminoacylase. L-AMPA was more effective (IC50 = 0.6 microM) than D-AMPA (IC50 = 4.8 microM) in displacing racemic [3H]AMPA from binding sites on rat

  谷氨酸中枢神经系统受体激动剂α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）的对映体是通过可重复使用的固定化氨酰酶通过动力学拆分外消旋N-乙酰化3-甲氧基衍生物制备的。L-AMPA可以比D-AMPA（IC50 = 4.8 microM）更有效（IC50 = 4.8 microM），以消除大鼠脑突触膜上结合位点的外消旋[3H] AMPA，并使其具有相对的体内兴奋性。
• Structural Analogues of Ibotenic Acid. Syntheses of 4-Methylhomoibotenic Acid and AMPA, Including the Crystal Structure of AMPA, Monohydrate.
  作者：Tage Honoré、Jørn Lauridsen、Olle Heby、Christer von Bahr、Hans Glaumann

  DOI：10.3891/acta.chem.scand.34b-0235

  日期：——
• Ibotenic acid analogs. Synthesis and biological and in vitro activity of conformationally restricted agonists at central excitatory amino acid receptors
  作者：Povl Krogsgaard-Larsen、Elsebet O. Nielsen、David R. Curtis

  DOI：10.1021/jm00371a005

  日期：1984.5

  A number of analogues of ibotenic acid [(RS)-3-hydroxy-5- isoxazoleglycine ] were synthesized; they were tested as excitants on neurons in the cat spinal cord, by using microelectrophoretic techniques, and as inhibitors of the binding of kainic acid (KA) in vitro, by using synaptic membranes prepared from rat brains. The excitatory effects of the 3- isoxazolol amino acids (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5, 4-c]pyridine-7-carboxylic acid (4, 7- HPCA ), (RS)-alpha-amino-3-hydroxy-5,6-dihydro-4H- cyclohept [1,2-d] isoxa zole - 8-propionic acid (8, 8- AHCP ), (RS)-alpha-amino-3- hydroxy-7,8-dihydro-6H- cyclohept [1,2-d] isoxazole -4-propionic acid (12, 4- AHCP ), and (RS)-alpha-(methylamino)-3-hydroxy-5-methyl- 4- isoxazolepropionic acid (15, N-Me-AMPA) were shown to be sensitive to (S)-glutamic acid diethyl ester (GDEE), an antagonist at quisqualic acid ( QUIS ) receptors, and insensitive to (RS)-2-amino-5-phosphonovaleric acid ( 2APV ), an antagonist at N-methyl-(R)-aspartic acid (NMDA) receptors. The compounds 4 and 12 proved to be particularly potent agonists at the former class of receptor, assumed to represent physiological glutamic acid receptors. The amino acids (RS)-beta-(2-carboxyphenyl)alanine (19), an analogue of 12, and (RS)-2-(3-carboxyphenyl) glycine were weak GDEE-sensitive excitants with potencies comparable with that of 8. All of the compounds were tested as inhibitors of KA binding. With the exception of 12 and 19, which showed very low affinity for the KA binding sites, the compounds studied were inactive in this in vitro test system.