(E)-2-氧代戊烯二酸二甲酯 | 38256-25-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (E)-2-氧代戊烯二酸二甲酯
• 英文名称: dimethyl (E)-2-oxoglutaconate
• 英文别名: dimethyl 2-oxoglutaconate；dimethyl 2-ketoglutaconate；dimethyl 4-oxoglutaconate；dimethyl trans-2-ketoglutaconate；dimethyl (E)-4-oxopent-2-enedioate；(E)-4-oxopent-2-enedioic acid dimethyl ester；(E)-dimethyl 4-oxopent-2-enedioate；Dimethyl 4-oxopent-2-enedioate
• CAS: 38256-25-6
• 化学式: C₇H₈O₅
• 分子量: 172.138
• InChiKey: AMBZDHXNCVCBRQ-ONEGZZNKSA-N

物化性质

• 沸点：
  241.6±32.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-2-氧代戊烯二酸二甲酯 在 四(三苯基膦)钯 、 2-甲基苯磺酸 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 dimethyl 6-phenylquinoline-2,4-dicarboxylate
  参考文献：
  名称：

  Synthesis and in Vitro Pharmacology of Substituted Quinoline-2,4-dicarboxylic Acids as Inhibitors of Vesicular Glutamate Transport

  摘要：

  The vesicular glutamate transport (VGLUT) system selectively mediates the uptake of L-glutamate into synaptic vesicles. Uptake is linked to an H+-ATPase that provides coupling among ATP hydrolysis, an electrochemical proton gradient, and glutamate transport. Substituted quinoline-2,4-dicarboxylic acids (QDCs), prepared by condensation of dimethyl keto-glutaconate (DKG) with substituted anilines and subsequent hydrolysis, were investigated as potential VGLUT inhibitors in synaptic vesicles. A brief panel of substituted QDCs was previously reported (Carrigan et al. Bioorg. Med. Chem. Lett. 1999, 9, 2607-2612), and showed that certain substituents led to more potent competitive inhibitors of VGLUT. Using these compounds as leads, an expanded series of QDC analogues were prepared either by condensation of DKG with novel anilines or via aryl-coupling (Suzuki or Heck) to dimethyl 6-bromoquino-linedicarboxylate. From the panel of almost 50 substituted QDCs tested as inhibitors of the VGLUT system, the 6-PhCH=CH-QDC (K-i = 167 muM), 6-PhCH2CH2-QDC (K-i = 143 muM), 6-(4'-phenylstyryl)-QDC (K-i = 64 AM), and 6-biphenyl-4-yl-QDC (K-i = 41 muM) were found to be the most potent blockers. A preliminary assessment of the key elements needed for binding to the VGLUT protein based on the structure-activity relationships for the panel of substituted QDCs is discussed herein. The substituted QDCs represent the first synthetically derived VGLUT inhibitors and are promising templates for the development of selective transporter inhibitors.

  DOI：

  10.1021/jm010261z
• 作为产物：
  描述：

  alpha-酮戊二酸 在 氯化亚砜 、 溴 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 (E)-2-氧代戊烯二酸二甲酯
  参考文献：
  名称：

  Synthesis and in Vitro Pharmacology of Substituted Quinoline-2,4-dicarboxylic Acids as Inhibitors of Vesicular Glutamate Transport

  摘要：

  The vesicular glutamate transport (VGLUT) system selectively mediates the uptake of L-glutamate into synaptic vesicles. Uptake is linked to an H+-ATPase that provides coupling among ATP hydrolysis, an electrochemical proton gradient, and glutamate transport. Substituted quinoline-2,4-dicarboxylic acids (QDCs), prepared by condensation of dimethyl keto-glutaconate (DKG) with substituted anilines and subsequent hydrolysis, were investigated as potential VGLUT inhibitors in synaptic vesicles. A brief panel of substituted QDCs was previously reported (Carrigan et al. Bioorg. Med. Chem. Lett. 1999, 9, 2607-2612), and showed that certain substituents led to more potent competitive inhibitors of VGLUT. Using these compounds as leads, an expanded series of QDC analogues were prepared either by condensation of DKG with novel anilines or via aryl-coupling (Suzuki or Heck) to dimethyl 6-bromoquino-linedicarboxylate. From the panel of almost 50 substituted QDCs tested as inhibitors of the VGLUT system, the 6-PhCH=CH-QDC (K-i = 167 muM), 6-PhCH2CH2-QDC (K-i = 143 muM), 6-(4'-phenylstyryl)-QDC (K-i = 64 AM), and 6-biphenyl-4-yl-QDC (K-i = 41 muM) were found to be the most potent blockers. A preliminary assessment of the key elements needed for binding to the VGLUT protein based on the structure-activity relationships for the panel of substituted QDCs is discussed herein. The substituted QDCs represent the first synthetically derived VGLUT inhibitors and are promising templates for the development of selective transporter inhibitors.

  DOI：

  10.1021/jm010261z

文献信息

• [EN] TREATMENT OF DISORDERS ASSOCIATED WITH OXIDATIVE STRESS AND COMPOUNDS FOR SAME<br/>[FR] TRAITEMENT DE TROUBLES ASSOCIÉS AU STRESS OXYDATIF ET COMPOSÉS CORRESPONDANTS
  申请人：UNIV ADELAIDE

  公开号：WO2021179049A1

  公开（公告）日：2021-09-16

  The present invention relates to the treatment of disorders associated with oxidative stress including neuropathic pain and small synthetically derived compounds for treating such disorders.

  本发明涉及治疗与氧化应激相关的疾病，包括神经性疼痛以及用于治疗这些疾病的小型合成化合物。
• Synthesis of Isomeric Analogues of Coenzyme Pyrroloquinoline Quinone (PQQ)
  作者：Zhoupeng Zhang、L. M. V. Tillekeratne、Richard A. Hudson

  DOI：10.1055/s-1996-4226

  日期：1996.3

  Three isomeric analogues 2-4 of the redox-active coenzyme 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid (1, PQQ, methoxatin) were synthesized from methoxynitroanilines 8, 9 and 10a, respectively. Reaction of the diazonium salts of each of the starting compounds with ethyl α-methylacetoacetate gave the corresponding substituted phenylhydrazones of ethyl pyruvate. These intermediates underwent acid-catalyzed Fischer indolization and gave the esters 13, 17 and 25, respectively. Reduction to the corresponding aminoindoles with hydrogen over Pd/C, followed by Doebner-von Miller quinoline synthesis with dimethyl trans-2-ketoglutaconate, oxidation of the intermediate methoxy compound to the o-quinone, and hydrolysis of triester products gave 2, 3, and 4, respectively. These isomers will serve as authentic examples to define their possible formation in nature and will also serve as isosteric probes to define the binding of PQQ at active sites in PQQ-requiring quinoproteins.

  三种氧化还原活性辅酶4,5-二氢-4,5-二氧-1H-吡咯并[2,3-f]喹啉-2,7,9-三羧酸（1，PQQ，甲氧嘧啶）的异构类似物2-4，分别从甲氧基硝基苯胺8、9和10a合成得到。各起始化合物的重氮盐与乙基α-甲基乙酰乙酸酯反应，得到相应的乙基丙酮酸取代苯脒。这些中间体在酸性催化下发生Fischer吲哚化反应，分别生成酯13、17和25。通过氢气在Pd/C上的还原得到相应的氨基吲哚，随后与二甲基反式2-氧戊二酸酯进行Doebner-von Miller喹啉合成，将中间甲氧基化合物氧化为邻醌，并水解三酯产物，分别得到2、3和4。这些异构体将作为天然形成可能性的真实例证，并作为等构探针来定义PQQ在需要PQQ的醌蛋白活性位点的结合。
• Synthese und Eigenschaften der Furo- und Thieno-Analogen von PQQ-Triester
  作者：Pierre Martin、Tammo Winkler

  DOI：10.1002/hlca.19940770113

  日期：1994.2.9

  Synthesis and Characterization of the Furo and Thieno Analogues of the Triester of PQQ

  PQQ三酯的呋喃和硫代诺类似物的合成与表征
• [EN] GLUCOSE TRANSPORT INHIBITORS<br/>[FR] INHIBITEURS DE TRANSPORT DU GLUCOSE
  申请人：BAYER PHARMA AG

  公开号：WO2016202898A1

  公开（公告）日：2016-12-22

  The present invention relates to chemical compounds that selectively inhibit glucose transporter 1 (GLUT1), to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

  本发明涉及选择性抑制葡萄糖转运蛋白1（GLUT1）的化合物，涉及制备该类化合物的方法，涉及包含该类化合物的药物组合物和药物组合物，涉及利用该类化合物制造用于治疗或预防疾病的药物组合物，以及用于制备该类化合物的中间化合物。
• Preparation and evaluation of sulfur-containing metal chelators
  作者：Sylvain Clavier、Øystein Rist、Stina Hansen、Lars-Ole Gerlach、Thomas Högberg、Jan Bergman

  DOI：10.1039/b307399h

  日期：——

  With a view to probe the structure and function of G-protein coupled receptors the synthesis of functionalized 8-mercaptoquinoline derivatives and 2-(2-pyridyl)thiophenol was achieved. A fluorescence-based method for determining the affinity of these metal chelators toward zinc ions was developed.

  为探究G蛋白偶联受体的结构和功能，成功合成了功能化的8-巯基喹啉衍生物和2-(2-吡啶基)苯并噻吩。开发了一种基于荧光的方法来测定这些金属螯合剂对锌离子的亲和力。