threo-β-Hydroxy-DL-asparaginsaeuredimethylester

• 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: threo-β-Hydroxy-DL-asparaginsaeuredimethylester
• 英文别名: D,L-threo-β-Hydroxyasparaginsaeure-dimethylester；dimethyl (2S,3S)-2-amino-3-hydroxybutanedioate
• 化学式: C₆H₁₁NO₅
• 分子量: 177.157
• InChiKey: FKPFNKFGJIMFFG-IMJSIDKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  threo-β-Hydroxy-DL-asparaginsaeuredimethylester 在 氨 作用下， 生成 threo-Hydroxy-DL-aspartic acid-diamid
  参考文献：
  名称：

  5-Carboxamido-4-amino-3-isoxazolidone, an asparagine analog

  摘要：

  trans-Aziridine-2,3-dicarboxylic ester was used to prepare the required beta-chlorohydroxamic acid used in the synthesis of the title compound. The trans configuration of the asparagine analogue was established by hydrogenolysis to erythro-beta-hydroxyasparagine amide. Neither the title compound nor the intermediate aziridinehydroxamic acid (8) showed significant activity against the L1210 and P-388 tumors. The title compound was inactive as an inhibitor of asparagine synthetase from Novikoff hepatoma and did not inhibit the growth of some 25 bacteria and fungi.

  DOI：

  10.1021/jm00205a026
• 作为产物：
  描述：

  (+/-)-(2R,3R)-dimethyl 2-(benzyloxycarbonylamino)-3-hydroxysuccinate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成 threo-β-Hydroxy-DL-asparaginsaeuredimethylester
  参考文献：
  名称：

  化学酶合成和功能表征的天冬氨酸类似物作为新型兴奋性氨基酸转运抑制剂的药理学表征

  摘要：

  天冬氨酸（Asp）衍生物是特权化合物，可用于研究谷氨酸能神经传递中兴奋性氨基酸转运蛋白（EAAT）的作用。在这里，我们报告了在C-3处带有（环）烷氧基和（杂）芳氧基取代基的各种Asp衍生物的合成。在EAAT1-4亚型中对它们的药理特性进行了表征。的升-苏-3-取代的天冬氨酸衍生物13A - ë和13克- ķ是nonsubstrate抑制剂，在表现出EAAT1-4锅活性与IC 50值范围为0.49至15μm。（dl - threo）-19a – c之间的比较和（DL -赤） - 19A - Ç天冬氨酸类似物证实，苏式配置是EAAT1-4抑制活性是至关重要的。1 -TFB-TBOA（3a）的类似物（3b - e）被证明是有效的EAAT1-4抑制剂，IC 50值为5至530 nM。非选择性EAAT抑制剂1 -TBOA与EAAT2选择性抑制剂WAY-213613或EAAT3优选抑制剂NBI-591

  DOI：

  10.1021/acs.jmedchem.8b00700

文献信息

• SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS
  申请人：GLAXOSMITHKLINE LLC

  公开号：US20150152108A1

  公开（公告）日：2015-06-04

  The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

  本发明涉及新型取代桥式脲化合物，相应的相关类似物，药物组合物以及其使用方法。本发明的抑制素调节化合物可用于延长细胞寿命，并治疗和/或预防各种疾病和疾病，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块疾病、炎症、癌症和/或潮红有关的疾病或疾病，以及那些会受益于增加线粒体活性的疾病或疾病。本发明还涉及包含抑制素调节化合物与另一治疗剂组合的组合物。
• β-Indolyloxy Functionalized Aspartate Analogs as Inhibitors of the Excitatory Amino Acid Transporters (EAATs)
  作者：Na Liu、Anders A. Jensen、Lennart Bunch

  DOI：10.1021/acsmedchemlett.0c00342

  日期：2020.11.12

  designed and synthesized the first β-indolyloxy Asp analogs 15a–d with the aim to probe a hitherto unexplored adjacent pocket to the substrate binding site. The pharmacological properties of 15a–d were characterized at hEAAT1-3 and rEAAT4 in a conventional [3H]-d-Asp uptake assay. Notably, thiophene analog 15b and the para-trifluoromethyl phenyl analog 15d were found to be hEAAT1,2-preferring inhibitors

  兴奋性氨基酸转运蛋白 (EAAT) 介导主要兴奋性神经递质l-谷氨酸 (Glu) 的摄取。这些转运蛋白在调节中枢 Glu 水平方面的基本功能使它们成为广泛的神经退行性疾病和精神疾病的有趣治疗靶点。l -天冬氨酸 (Asp) 是另一种 EAAT 底物，已作为开发 EAAT 抑制剂的特殊支架。在这项研究中，我们设计并合成了第一个 β-吲哚氧基 Asp 类似物15a – d，目的是探测一个迄今为止尚未探索的与底物结合位点相邻的口袋。15a - d的药理特性在常规[ 3 H] -d- Asp 摄取测定中在hEAAT1-3 和rEAAT4 处表征。值得注意的是，噻吩类似物15B和对三氟甲基苯基模拟15D被发现被hEAAT1,2-宁愿抑制剂表现出的IC 50个在这两个转运值在高纳摩尔范围内（0.21-0.71μM）对IC 50个在低微摩尔值EAAT3,4 (1.6–8.9 μM) 的范围。总之，本文提
• <i>threo</i>- and <i>erythro</i>- β-Hydroxy-<scp>DL</scp>-aspartic acids
  作者：Clifton W. Jones III、Donald E. Leyden、Charles H. Stammer

  DOI：10.1139/v69-722

  日期：1969.12.1

  An improved procedure for the synthesis of threo- and erythro-β-hydroxy-DL-aspartic acids is described. An nuclear magnetic resonance study of both diastereomers indicated that the threo isomer exists primarily as the conformer having anti carboxyl groups while the erythro compound prefers a conformation with gauche carboxyl functions. Possible reasons for this anomaly are presented.

  本文描述了一种改进的合成threo-和erythro-β-羟基-DL-天冬氨酸的方法。对两个对映异构体的核磁共振研究表明，threo异构体主要存在于具有反式羧基的构象中，而erythro化合物则更喜欢具有左旋羧基功能的构象。本文还提出了可能导致这种异常的原因。
• Divergent synthesis of biologically active l-threo-β-hydroxyaspartates from common trans-oxazolidine dicarboxylate
  作者：Yoonjae Lee、Youngran Seo、Boram Lee、Hyuenyoung Kwon、Kyungsu Chung、Young Gyu Kim

  DOI：10.1007/s00726-022-03196-8

  日期：2022.12

  A divergent synthetic strategy starting from a common trans-oxazolidine dicarboxylate intermediate has been successful to produce several non-proteinogenic l-threo-β-hydroxyaspartate derivatives efficiently with high stereoselectivity. Three bioactive α-amino-β-hydroxy acids, l-threo-β-hydroxyaspartic acid, l-threo-β-hydroxyasparagine, and l-threo-β-benzyloxyaspartic acid, were synthesized in good

  从常见的反式-恶唑烷二羧酸中间体开始的不同合成策略已成功地以高立体选择性高效地生产几种非蛋白原性l-苏型-β-羟基天冬氨酸衍生物。三种具有生物活性的α-氨基-β-羟基酸，l-苏型-β-羟基天冬氨酸，l-苏型-β-羟基天冬酰胺， l-苏型-β-羟基天冬酰胺-β-苄氧基天冬氨酸，由常见的手性中间体以良好的产率 (58–83%) 合成，以及在常见中间体的 α-氨基、β-羟基或 α-羧酸处形成化学选择性肽键由于手性中间体上的正交保护基团，有可能以 46~77% 的产率（三到四步）提供相应的二肽、三肽或二缩肽中间体。
• Substituted bridged urea analogs as sirtuin modulators
  申请人：GLAXOSMITHKLINE LLC

  公开号：US10590135B2

  公开（公告）日：2020-03-17

  The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

  本发明涉及新型取代桥基脲化合物、相应的相关类似物、药物组合物及其使用方法。本发明的Sirtuin调节化合物可用于增加细胞的寿命，治疗和/或预防多种疾病和失调，这些疾病和失调包括但不限于例如与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、凝血障碍、炎症、癌症和/或潮红有关的疾病或失调，以及将受益于线粒体活性增加的疾病或失调。本发明还涉及由sirtuin调节化合物与另一种治疗剂组合而成的组合物。