(2R,4R)-4-甲基谷氨酸 | 2596-04-5

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 谷氨酸类衍生物
• 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: (2R,4R)-4-甲基谷氨酸
• 英文名称: (+/-)-(2S,4S)-4-methylglutamic acid
• 英文别名: (4R)-4-Methyl-D-glutamic acid；(2R,4R)-2-amino-4-methylpentanedioic acid
• CAS: 2596-04-5；6141-27-1；14561-55-8；31137-74-3；34605-34-0；34605-35-1；38523-28-3；59685-03-9；62278-76-6；77842-39-8；97550-62-4；97550-63-5
• 化学式: C₆H₁₁NO₄
• 分子量: 161.158
• InChiKey: KRKRAOXTGDJWNI-QWWZWVQMSA-N

物化性质

• 熔点：
  178 °C
• 沸点：
  287.44°C (rough estimate)
• 密度：
  1.3482 (rough estimate)
• 溶解度：
  H2O: >10 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  5

制备方法与用途

生物活性

SYM 2081 是一种有效且高选择性的红藻氨酸受体（kainate receptor）激动剂，能够抑制 [3H]-kainate 的结合，其 IC50 值为 35 nM。该化合物对 kainate 受体的选择性分别是 AMPA 和 NMDA 受体的 3000 倍和 200 倍。

靶点

IC50: 35 nM (kainate receptors)

反应信息

• 作为产物：
  描述：

  4-甲基谷氨酸 生成 (2R,4R)-4-甲基谷氨酸
  参考文献：
  名称：

  Resolution and regioselective protection of glutamic acid analogues. I- resolution of diastereomeric α-boroxazolidone derivatives.

  摘要：

  Diastereomeric alpha-boroxazolidone gamma-phenylethylamide (or gamma-phenylethanolamide) derivatives of 2-, 3- or 4-substituted glutamic acid analogues have been separated by silicagel chromatography, resulting, after deprotection, in a practical method for the resolution of most of these unnatural amino acids.

  DOI：

  10.1016/0957-4166(94)80036-7

文献信息

• 2,8′-Disubstituted-1,1′-Binaphthyls: A New Pattern in Chiral Ligands
  作者：Štěpán Vyskočil、Luděk Meca、Iva Tišlerová、Ivana Císařová、Miroslav Polášek、Syuzanna R. Harutyunyan、Yuri N. Belokon、Russel M. J. Stead、Louis Farrugia、Stephen C. Lockhart、William L. Mitchell、Pavel Kočovský

  DOI：10.1002/1521-3765(20021018)8:20<4633::aid-chem4633>3.0.co;2-n

  日期：2002.10.18

  The title binaphthyls 19 and 26, which are the positional isomers of 2-methoxy-2'-(diphenylphosphino)-1,1'-binaphthyl (MOP, 19) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN, 26), have been synthesized by Suzuki coupling as the key step (10 + 15 --> 18), followed by functional group transformations, involving C-P and C-N bond formation (18 --> 19 and 18 --> 23). Racemic intermediate 22 was resolved by co-crystallization with N-benzylcinchonidinium chloride and the absolute configuration determined by X-ray crystallography. These novel binaphthyls are configurationally stable and, as such, potentially usable as chiral ligands in asymmetric reactions. Michael addition of the glycine-derived enolate 40 to methyl acrylate, carried out in the presence of (R)-(-)-27 as the chiral phase-transfer catalyst, afforded L-glutamic acid (S)-(+)-43 of 92% ee (after hydrolysis of the primary product).
• Synthesis, Resolution, and Biological Evaluation of the Four Stereoisomers of 4-Methylglutamic Acid: Selective Probes of Kainate Receptors
  作者：Zi-Qiang Gu、David P. Hesson、Jeffrey C. Pelletier、Maria-Luisa Maccecchini、Li-Ming Zhou、Phil Skolnick

  DOI：10.1021/jm00014a002

  日期：1995.7
• ALKYLCARBOXY AMINO ACIDS-MODULATORS OF THE KAINATE RECEPTOR
  申请人：Bearsden Bio, Inc.

  公开号：EP0809624B1

  公开（公告）日：2001-08-29
• US5731348A
  申请人：——

  公开号：US5731348A

  公开（公告）日：1998-03-24
• [EN] ALKYLCARBOXY AMINO ACIDS-MODULATORS OF THE KAINATE RECEPTOR<br/>[FR] MODULATEURS A BASE D'AMINOACIDES ALKYLCARBOXY DU RECEPTEUR DE KANAITE
  申请人：——

  公开号：WO1996025387A1

  公开（公告）日：1996-08-22

  [EN] Compounds of a class of alkyl carboxy amino acid analogs of glutamic acid according to formula I act as specific regulators of kainic acid EAA receptor cation channel, wherein R<1> is 1) CH3, or 2) halogen; R<2> and R<3> are independently 1) H, 2) C1-C6-alkyl, 3) C3-C4-alkenyl, 4) C3-C5-cycloalkyl, 5) C1-C6-alkyl-CO-, 6) C1-C6-alkyl-OCO-, 7) C1-C6-alkyl-NHCO-, 8) CHO-, or 9) C3-C6-alkynyl; R<2> and R<3> taken together can be -CH2(CH2)pCH2-; p is 0, 1, 2 or 3; and pharmaceutically acceptable salts of these compounds, but not including compounds of Formula I wherein R<2> and R<3> are H and R<1> is CH3 or R<1> is F. These compounds are useful for treating neurological, neuropsychological, neuropsychiatric, neurodegenerative, neuropsychopharmacological and functional disorders associated with excessive or insufficient activation of the kainic acid subtype of the ionotropic EAA receptors; treating cognitive disorders associated with deactivation, suboptimal activation or over-activation of the kainic acid receptor; alleviating pain and improving and enhancing memory, learning, and associated mental processes. A method for designing novel AMPA or kainic acid receptor agonists or antagonists is also disclosed.
  [FR] Des composés appartenant à une nouvelle classe d'analogues d'aminoacides alkylcarboxy d'acide glutamique, de la formule (I), agissent comme régulateurs spécifiques du canal cationique du récepteur d'aminoacides excitateurs (EAA) d'acide kaïnique. Dans cette formule, R<1> représente 1) CH3 ou 2) halogène; R<2> et R<3> représentent indépendamment 1) H, 2) alkyle C1-C6, 3) alcényle C3-C4, 4) cycloalkyle C3-C5, 5) alkyle C1-C6-CO-, 6) alkyle C1-C6-OCO-, 7) alkyle C1-C6-NHCO-, 8) CHO- ou 9) alcynyle C3-C6; R<2> et R<3> peuvent représenter ensemble -CH2(CH2)pCH2-; p vaut 0, 1, 2 ou 3. L'invention concerne également les sels pharmaceutiquement acceptables de ces composés, hormis les composés de la formule (I) où R<2> et R<3> représentent H et R<1> représente CH3 ou F. Ces composés permettent de traiter des troubles neurologiques, neuropsychologiques, neuropsychiatriques, neurodégénératifs, neuropsychopharmacologiques et fonctionnels associés à une activation excessive ou insuffisante du sous-type acide kaïnique des récepteurs EAA ionotropes; de traiter des troubles cognitifs associés à la désactivation, l'activation sous-optimale ou la sur-activation du récepteur d'acide kaïnique; de soulager les douleurs et d'améliorer la mémoire, l'apprentissage et les processus mentaux associés. Un procédé de conception de nouveaux agonistes ou antagonistes du récepteur d'acide kaïnique ou AMPA est également décrit.