ACPT-II | 195209-04-2

• 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: ACPT-II
• 英文别名: (1R,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid
• CAS: 195209-04-2
• 化学式: C₈H₁₁NO₆
• 分子量: 217.178
• InChiKey: FERIKTBTNCSGJS-OCDMWJSJSA-N

物化性质

• 沸点：
  440.4±45.0 °C(Predicted)
• 密度：
  1.651±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：5mg/mL； DMSO：0.25mg/mL； PBS pH 7.2：10 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -1.04
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  137.92
• 氢给体数：
  4.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ACPT-II 在 盐酸 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 509.0h， 生成 (1R,3R,4S)-trimethyl N-t-Boc-1-aminocyclopentane-1,3,4-tricarboxylic ester
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Aminocyclopentanetricarboxylic Acids:  New Tools to Discriminate between Metabotropic Glutamate Receptor Subtypes

  摘要：

  The four stereoisomers of 1-aminocyclopentane-1,3,4-tricarboxylic acid {ACPT-I (18) and -II (19), (3R,4R)-III [(-)-20], and (3S,4S)-III [(+)-20]} have been synthesized and evaluated for their effects at glutamate receptors subtypes. ACPTs are ACPD analogues in which a third carboxylic group has been added at position 4 in the cyclopentane ring. None of the ACPT isomers showed a significant effect on ionotropic NMDA, KA, and AMPA receptors. On the other hand, ACPT-II (19) was found to be a general competitive antagonist for metabotropic receptors (mGluRs) and exhibited a similar affinity for mGluRla (K-B = 115 +/- 2 mu M), mGluR2 (K-B = 88 +/- 21 mu M), and mGluR4a (K-B = 77 +/- 9 mu M), the representative members-of group I, II and III mGluRs, respectively. Two other isomers, ACPT-I (18) and (+)-(3S,4S)-ACPT-III [(+)-20], were potent agonists at the group III receptor mGluRAa (EC50 = 7.2 +/- 2.3 and 8.8 +/- 3.2 mu M) and competitive antagonists with low affinity for mGluR1a and mGluR2 (K-B > 300 mu M). Finally, (-)-(3R,4R)-ACPT-III [(-)-20] was a competitive antagonist with poor but significant affinity for mGluR4a (K-B = 220 mu M). These results demonstrate that the addition of a third carboxylic group to ACPD can change its activity (from agonist to antagonist) and either increase or decrease its selectivity and/or affinity for the various mGluR subtypes.

  DOI：

  10.1021/jm970207b
• 作为产物：
  描述：

  2,4-dioxo-1,3-diazaspiro[4.4]nonane-7,8-dicarboxylic acid 在 4-二甲氨基吡啶 、 lithium hydroxide 作用下， 以 乙腈 为溶剂， 反应 6.5h， 生成 ACPT-II
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Aminocyclopentanetricarboxylic Acids:  New Tools to Discriminate between Metabotropic Glutamate Receptor Subtypes

  摘要：

  The four stereoisomers of 1-aminocyclopentane-1,3,4-tricarboxylic acid {ACPT-I (18) and -II (19), (3R,4R)-III [(-)-20], and (3S,4S)-III [(+)-20]} have been synthesized and evaluated for their effects at glutamate receptors subtypes. ACPTs are ACPD analogues in which a third carboxylic group has been added at position 4 in the cyclopentane ring. None of the ACPT isomers showed a significant effect on ionotropic NMDA, KA, and AMPA receptors. On the other hand, ACPT-II (19) was found to be a general competitive antagonist for metabotropic receptors (mGluRs) and exhibited a similar affinity for mGluRla (K-B = 115 +/- 2 mu M), mGluR2 (K-B = 88 +/- 21 mu M), and mGluR4a (K-B = 77 +/- 9 mu M), the representative members-of group I, II and III mGluRs, respectively. Two other isomers, ACPT-I (18) and (+)-(3S,4S)-ACPT-III [(+)-20], were potent agonists at the group III receptor mGluRAa (EC50 = 7.2 +/- 2.3 and 8.8 +/- 3.2 mu M) and competitive antagonists with low affinity for mGluR1a and mGluR2 (K-B > 300 mu M). Finally, (-)-(3R,4R)-ACPT-III [(-)-20] was a competitive antagonist with poor but significant affinity for mGluR4a (K-B = 220 mu M). These results demonstrate that the addition of a third carboxylic group to ACPD can change its activity (from agonist to antagonist) and either increase or decrease its selectivity and/or affinity for the various mGluR subtypes.

  DOI：

  10.1021/jm970207b

文献信息

• Trans Pyrrolidinyl Derivates and Their Pharmaceutical Use
  申请人：Schann Stephan

  公开号：US20080027127A1

  公开（公告）日：2008-01-31

  The present invention relates to the use of trans pyrrolidinyl of the formula (I) or (II) in which: R 1 , R 2 or R 3 are hydrogen or a carboxy or amino protecting group; R 4 to R 8 represent hydrogen or an alkyl radical; R 9 represents a (R 10 ) n (—R 11 ) m group wherein R 10 is —CO—, —CS—, —O—, —S—, —SO—, —SO 2 —, —COO—, —CONR a —, —N(R a )CO—, —CSNR a —, —N(R a )CS—, —N(R a )—, R b , aryl, and R 11 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）的反式吡咯烷基，其中：R1、R2或R3为氢或羧基或氨基保护基；R4至R8表示氢或烷基基团；R9表示（R10）n（—R11）m基团，其中R10为—CO—、—CS—、—O—、—S—、—SO—、—SO2—、—COO—、—CONRa—、—N（Ra）CO—、—CSNRa—、—N（Ra）CS—、—N（Ra）—、Rb、芳基，而R11为极性基团，用于治疗和/或预防与改变谷氨酸能信号和/或功能相关的疾病和/或可以受到哺乳动物谷氨酸水平或信号改变影响的疾病。
• 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。
• REGULATION OF NEURONAL FUNCTION THROUGH METABOTROPIC GLUTAMATE RECEPTOR SIGNALING PATHWAYS
  申请人：Liu Feng

  公开号：US20060223158A1

  公开（公告）日：2006-10-05

  The present invention provides methods and compositions for modulating the activities of metabotropic glutamate receptor intracellular signaling molecules. The present invention provides methods and compositions for modulating the activities of casein kinase I and/or cyclin-dependent kinase 5 in cells or tissues. The present invention provides methods of modulating the function of calcium channels in cells or tissues. The present invention provides methods of treating calcium channel dysfunction. The present invention provides methods of identifying agents that modulate the activities of the metabotropic glutamate receptor intracellular signaling molecules casein kinase I and/or cyclin-dependent kinase 5 for use in such treatments.

  本发明提供了调节代谢型谷氨酸受体胞内信号分子活性的方法和组合物。本发明提供了调节细胞或组织中酪蛋白激酶 I 和/或细胞周期蛋白依赖性激酶 5 活性的方法和组合物。本发明提供了调节细胞或组织中钙离子通道功能的方法。本发明提供了治疗钙通道功能障碍的方法。本发明提供了鉴定调节代谢型谷氨酸受体胞内信号分子酪蛋白激酶I和/或细胞周期蛋白依赖性激酶5活性的制剂用于此类治疗的方法。
• INDUCTION OF ANALGESIA IN NEUROPATHIC PAIN
  申请人：The University Court Of The University of Edinburgh

  公开号：EP2046358B1

  公开（公告）日：2015-07-22
• Combining BACE1 Inhibitors With mGluR Agonists For Alzheimer's Disease Therapy
  申请人：University of Connecticut

  公开号：US20210161910A1

  公开（公告）日：2021-06-03

  Disclosed pharmaceutical compositions including a Beta site APP Cleaving Enzyme (BACE1) inhibitor and an metabotropic glutamate receptor (mGluR) agonist, and methods for use of such compositions to treat Alzheimer's disease (AD), Down's syndrome, Parkinson's disease, vascular dementia, Dementia with Lewy Bodies, dementia, and/or frontal temporal dementia.