(2R,4R)-4-氨基-2,4-吡咯烷二甲酸 | 169209-63-6

• 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-氨基-2,4-吡咯烷二甲酸
• 中文别名: (2R,4R)-4-氨基吡咯烷-2,4-二羧酸酯(2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate
• 英文名称: (2R,4R)-4-amino-4-carboxyproline
• 英文别名: (2R,4R)-APDC；(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid；2R,4R-4-aminopyrrolidine-2,4-dicarboxylate；(2R,4R) 4-aminopyrrolidine-2,4-dicarboxylic acid
• CAS: 169209-63-6
• 化学式: C₆H₁₀N₂O₄
• mdl: MFCD00672677
• 分子量: 174.156
• InChiKey: XZFMJVJDSYRWDQ-AWFVSMACSA-N

物化性质

• 溶解度：
  H2O：≥2mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -6.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  6

制备方法与用途

生物活性

(2R,4R)-APDC 是一种选择性的 II 类代谢型谷氨酸受体 (mGluRs)，具有抗惊厥和神经保护作用。

靶点

| 分组II mGlu受体 |

体内研究

2R, 4R-APDC（1-10 nmol；脑室内给药，连续14天）可减少海马齿状回的细胞增殖。具体实验结果显示：

• 动物模型：成年雄性Sprague-Dawley大鼠，体重在300至350 g之间
• 剂量：1 nmol/10 μl 或 10 nmol/10μl
• 给药方式：脑室内给药（ICV），每天一次，共14天
• 结果：导致海马区BrdU免疫活性细胞减少

反应信息

• 作为反应物：
  描述：

  (2R,4R)-4-氨基-2,4-吡咯烷二甲酸 在 sodium hydroxide 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 (2R,4r)-1-苄基-4-氨基-吡咯烷-2,4-二羧酸
  参考文献：
  名称：

  Synthesis, molecular modeling, and biology of the 1-benzyl derivative of APDC-an apparent mGluR6 selective ligand

  摘要：

  The synthesis of the 1-benzyl derivative of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid (1-benzyl-APDC) starting from cis-4-hydroxy-D-proline is disclosed together with a study of the activity of this compound at metabotropic glutamate receptors (mGluRs). The compound was found to display good mGluR6 selectivity, and may thus be a useful pharmacological research tool. (C) 1997 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)00068-1
• 作为产物：
  描述：

  ethyl (8R)-7-benzyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonane-8-carboxylate 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 氯化亚砜 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、413.69 kPa 条件下， 反应 5.0h， 生成 (2R,4R)-4-氨基-2,4-吡咯烷二甲酸
  参考文献：
  名称：

  Synthesis of the Four Isomers of 4-Aminopyrrolidine-2,4-dicarboxylate:  Identification of a Potent, Highly Selective, and Systemically-Active Agonist for Metabotropic Glutamate Receptors Negatively Coupled to Adenylate Cyclase

  摘要：

  The four isomers of 4-aminopyrrolidine-2,4-dicarboxylate (APDC) were prepared and evaluated for their effects at glutamate receptors in vitro. (2R,4R)-APDC (2a), an aza analog of the nonselective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD, 1), was found to possess relatively high affinity for metabotropic glutamate receptors (mGluRs) (ACPD-sensitive [H-3]glutamate binding IC50 = 6.49 +/- 1.21 mu M) with no effects on radioligand binding to NMDA, AMPA, or kainate receptors up to 100 mu M. None of the other APDC isomers showed significant mGluR binding affinity, indicating that this interaction is highly stereospecific. Both 1 and 2a were effective in decreasing forskolin-stimulated cAMP formation in the adult rat cerebral cortex (EC(50) = 8.17 +/- 2.21 mu M for 1; EC(50) = 14.51 +/- 5.54 mu M for 2a); however, while 1 was also effective in stimulating basal tritiated inositol monophosphate production in the neonatal rat cerebral cortex (EC(50) = 27.7 +/- 5.2 mu M), 2a (up to 100 mu M) was ineffective in stimulating phosphoinositide hydrolysis in this tissue preparation, further supporting our previous observations that 2a is a highly selective agonist for mGluRs negatively coupled to adenylate cyclase. Microelectrophoretic application of either 1 or 2a to intact rat spinal neurons produced an augmentation of AMPA-induced excitation (95 +/- 10% increase for 1, 52 +/- 6% increase for 2a). Intracerebral injection of 1 (400 nmol) produced characteristic limbic seizures in mice which are not mimicked by 2a (200-1600 nmol, ic). However, the limbic seizures induced by 1 were blocked by systemically administered 2a in a dose-dependent manner (EC(50) = 271 mg/kg, ip). It is concluded that (2R,4R)-APDC (2a) is a highly selective, systemically-active agonist of mGluRs negatively coupled to adenylate cyclase and that selective activation of these receptors in vivo can result in anticonvulsant effects.

  DOI：

  10.1021/jm9601765

文献信息

• Potentiators of glutamate receptors
  申请人：——

  公开号：US20040006114A1

  公开（公告）日：2004-01-08

  The present invention relates to potentiators of metabotropic glutamate receptor function and specifically provides compounds of formula I, compositions thereof and methods of using the same. 1

  本发明涉及代谢型谷氨酸受体功能的增强剂，具体提供了化合物I的公式、其组合物以及使用方法。
• PAK INHIBITORS FOR THE TREATMENT OF CELL PROLIFERATIVE DISORDERS
  申请人：AFRAXIS, INC.

  公开号：US20130116263A1

  公开（公告）日：2013-05-09

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of cell proliferative disorders and/or CNS disorders.

  本文提供了PAK抑制剂以及利用PAK抑制剂治疗细胞增殖性疾病和/或中枢神经系统疾病的方法。
• [EN] TRANS PYRROLIDINYL DERIVATIVES AND THEIR PHARMACEUTICAL USE<br/>[FR] DERIVES DE TRANS PYRROLIDINYLE ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：FAUST PHARMACEUTICALS

  公开号：WO2005118533A1

  公开（公告）日：2005-12-15

  The present invention relates to the use of trans pyrrolidinyl of the formula (I) or (II) in which: R1, R2 or R3 are hydrogen or a carboxy or amino protecting group; R4 to R8 represent hydrogen or an alkyl radical; R9 represents a (R10)n(-R11)m group wherein R10 is -CO-, -CS-, -O-, -S-, -SO-, -SO2-, -COO-, -CONRa-, -N(Ra)CO-, -CSNRa-, -N(Ra)CS-, -N(Ra)-, Rb, aryl, and R11 is a polar group, for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals.

  本发明涉及使用式（I）或（II）的trans吡咯烷基，其中：R1、R2或R3是氢或羧基或氨基保护基；R4至R8代表氢或烷基基团；R9代表（R10）n（-R11）m基团，其中R10是-CO-、-CS-、-O-、-S-、-SO-、-SO2-、-COO-、-CONRa-、-N(Ra)CO-、-CSNRa-、-N(Ra)CS-、-N(Ra)-、Rb、芳基，R11是一个极性基团，用于治疗和/或预防与改变谷氨酸能信号和/或功能有关的疾病，以及可以通过改变哺乳动物体内谷氨酸水平或信号传导而受影响的疾病。
• THIENOPYRIMIDINE AND THIENOPYRIDINE KINASE MODULATORS
  申请人：Gaul David Michael

  公开号：US20060281768A1

  公开（公告）日：2006-12-14

  The invention is directed to thienopyrimidines and thienopyridines compounds of Formula I and Formula II: where R 1 , R 3 , B, Z, Q, p, q and X are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3, the use of such compounds to reduce or inhibit kinase activity of FLT3 in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

  该发明涉及Formula I和Formula II的噻吩嘧啶和噻吩吡啶化合物：其中R1、R3、B、Z、Q、p、q和X的定义如本文所述，这些化合物的用途作为蛋白酪氨酸激酶调节剂，特别是FLT3的抑制剂，这些化合物的用途是减少或抑制细胞或受试者中FLT3的激酶活性，以及这些化合物的用途用于预防或治疗受试者的细胞增殖紊乱和/或与FLT3相关的紊乱。本发明进一步涉及包含本发明化合物的药物组合物，以及用于治疗癌症和其他细胞增殖紊乱等病症的方法。
• [EN] PAK INHIBITORS FOR THE TREATMENT OF CELL PROLIFERATIVE DISORDERS<br/>[FR] INHIBITEURS DE PAK POUR LE TRAITEMENT DE TROUBLES DE PROLIFÉRATION CELLULAIRE
  申请人：AFRAXIS INC

  公开号：WO2013067423A1

  公开（公告）日：2013-05-10

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of cell proliferative disorders and/or CNS disorders.

  本文提供PAK抑制剂和利用PAK抑制剂治疗细胞增殖性疾病和/或中枢神经系统疾病的方法。