(RS)-2-amino-4-(3-hydroxy-5-methyl-4-isoxazolyl)butyric acid | 179169-88-1

• 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-4-(3-hydroxy-5-methyl-4-isoxazolyl)butyric acid
• 英文别名: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl) butyric acid；homo-AMPA；2-amino-4-(5-methyl-3-oxo-1,2-oxazol-4-yl)butanoic acid
• CAS: 179169-88-1
• 化学式: C₈H₁₂N₂O₄
• 分子量: 200.194
• InChiKey: NZDIZJGEDFARSV-UHFFFAOYSA-N

物化性质

• 密度：
  1.327±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.03
• 重原子数：
  14.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  109.58
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (RS)-2-amino-4-(3-hydroxy-5-methyl-4-isoxazolyl)butyric acid 生成 (R)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid
  参考文献：
  名称：

  (S)-Homo-AMPA, a Specific Agonist at the mGlu₆ Subtype of Metabotropic Glutamic Acid Receptors

  摘要：

  Our previous publication (J. Med. Chem. 1996, 39, 3188-3194) described (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (Homo-AMPA) as a highly selective agonist at the mGlu(6) subtype of metabotropic excitatory amino acid (EAA) receptors. Homo-AMPA has already become a standard agonist for the pharmacological characterization of mGlu(6) (Trends Pharmacol. Sci. Suppl. 1997, 37-39), and we here report the resolution, configurational assignment, and pharmacology of (S)- (6) and (R)- (7) Homo-AMPA. Using the ''Ugi four-component condensation'', 3-(3-ethoxy-5-methylisoxazol-4-yl)propanal (10) was converted into the separable diastereomeric derivatives of 6 and 7, compounds 12 and 11, respectively. Deprotection of 12, in one or two steps, gave extensively racemized 6, which was converted in low yield into 6 (99.0% ee) through several crystallizations. 6 (99.7% ee) and 7 (99.9% ee) were finally obtained by preparative chiral HPLC. The configurational assignments of 6 and 7 were based on H-1 NMR spectroscopic studies on 12 and 11, respectively, and circular dichroism studies on 6 and 7. Values of optical rotations using different solvents and the chiral HPLC elution order of 6 and 7 supported the results of the spectroscopic configurational assignments. The activities of 6 and 7 at ionotropic EAA (iGlu) receptors and at mGlu(1-7) were studied. (S)-Homo-AMPA (6) was shown to be a specific agonist at mGlu(6) (EC50 = 58 +/- 11 mu M) comparable in potency with the endogenous mGlu agonist (S)-glutamic acid (EC50 = 20 +/- 3 mu M). Although Homo-AMPA did not show significant effects at iGlu receptors, (R)-Homo-AMPA (7), which was inactive at mGlu(1-7), turned out to be a weak N-methyl-D-aspartic acid (NMDA) receptor antagonist (IC50 = 131 +/- 18 mu M).

  DOI：

  10.1021/jm9703597
• 作为产物：
  描述：

  (RS)-5-<2-(3-methoxy-5-methyl-4-isoxazolyl)ethyl>hydantoin 在 盐酸 作用下， 反应 48.0h， 生成 (RS)-2-amino-4-(3-hydroxy-5-methyl-4-isoxazolyl)butyric acid
  参考文献：
  名称：

  Design, synthesis and pharmacology of model compounds for indirect elucidation of the topography of AMPA receptor sites

  摘要：

  Based on structure-activity studies on excitatory amino acids with specific agonist effect at (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptors we have earlier proposed a simple model of the AMPA receptor pharamacophore. In order to judge the capacity of this empirical model we have now synthesized and tested 3 model compounds derived from the AMPA receptor agonists, AMPA and (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HCPA). These model compounds, (RS)-2-amino-3-(5-ethyl-3-hydroxy-4-isoxazolyl)propionic acid (Et-AMPA), (RS)-2-amino-4-(3-hydroxy-5-methyl-4-isoxazolyl)butyric acid (Homo-AMPA) and (RS)-3-hydroxy-5,6,7,8-tetrahydro-4H-isoxazolo[5,4-c]azepine-8-carboxylic acid (Homo-7-HCPA) were tested electrophysiologically and in receptor binding assays. Et-AMPA was slightly more potent than AMPA as an AMPA agonist (EC50 = 2.3 muM compared to 3.5 muM for AMPA) and as a specific inhibitor of [H-3]AMPA binding (IC50 = 0.030 muM compared with 0.040 muM for AMPA), whereas Homo-AMPA was essentially inactive. Homo-7-HPCA was much weaker than 7-HPCA. These data support the view that the AMPA recognition site(s) comprise a confined region, which tightly binds the charged structure-elements of agonists molecules, and a cavity capable of accommodating bulky lipophilic groups in such compounds.

  DOI：

  10.1016/0223-5234(93)90114-t

文献信息

• A New Highly Selective Metabotropic Excitatory Amino Acid Agonist:  2-Amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric Acid
  作者：Hans Bräuner-Osborne、Frank A. Sløk、Niels Skjærbæk、Bjarke Ebert、Naohiro Sekiyama、Shigetada Nakanishi、Povl Krogsgaard-Larsen

  DOI：10.1021/jm9602569

  日期：1996.1.1

  homologous series of acidic amino acids, ranging from aspartic acid (1) to 2-aminosuberic acid (5), and the corresponding series of 3-isoxazolol bioisosteres of these amino acids, ranging from (RS)-2-amino-2-(3-hydroxy-5-methylisoxazol-4-yl)acetic acid (AMAA, 6) to (RS)-2-amino-6-(3-hydroxy-5-methylisoxazol-4-yl)hexanoic acid (10), were tested as ligands for metabotropic excitatory amino acid receptors (mGlu1

  从天冬氨酸（1）到2-氨基异丁烯酸（5）的酸性氨基酸的同源序列以及这些氨基酸的相应的3-isoxazolol生物异构体的序列，从（RS）-2-amino-2- （3-羟基-5-甲基异恶唑-4-基）乙酸（AMAA，6）至（RS）-2-氨基-6-（3-羟基-5-甲基异恶唑-4-基）己酸（10），将其作为代谢型兴奋性氨基酸受体（mGlu1 alpha，mGlu2，mGlu4a和mGlu6）的配体进行测试。而AMAA（6）和（RS）-2-氨基-3-（3-羟基-5-甲基异恶唑-4-基）丙酸（AMPA，7）是对N-甲基-D-天冬氨酸有效且高度选择性的激动剂酸（NMDA）和AMPA受体，分别是AMPA（7），（RS）-2-氨基-4-（3-羟基-5-甲基异恶唑-4-基）丁酸（homo-AMPA，8）的较高同源物），对离子型兴奋性氨基酸受体无活性。Homo-AMPA（8），然而，它是2-氨基己二酸的3-is
• Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions
  申请人：Kõster Hubert

  公开号：US20100248264A1

  公开（公告）日：2010-09-30

  Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Automated systems for performing the methods also are provided.

  提供了捕获化合物及其集合以及使用这些化合物进行生物分子分析的方法。特别地，提供了用于分析复杂蛋白质混合物（如蛋白质组）的集合、化合物和方法。这些化合物是多功能试剂，可用于分离和分离复杂的蛋白质混合物。还提供了执行这些方法的自动化系统。
• Anticonvulsive pharmaceutical compositions
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP1927348A1

  公开（公告）日：2008-06-04

  The present invention pertains to pharmaceutical compositions comprising, as the active ingredients, a combination of vigabatrin and of at least one glutamate receptor activating substance.

  本发明涉及药物组合物，其活性成分包括维加巴曲林和至少一种谷氨酸受体激活物质。
• REGULATION OF NEURONAL FUNCTION THROUGH METABOTROPIC GLUTAMATE RECEPTOR SIGNALING PATHWAYS
  申请人：THE ROCKEFELLER UNIVERSITY

  公开号：EP1404864A2

  公开（公告）日：2004-04-07
• EP1404864A4
  申请人：——

  公开号：EP1404864A4

  公开（公告）日：2008-05-28