4-[[2-(3,4-dihydroxyphenyl)ethyl]amino]-4-oxobutanoic acid | 137476-48-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-[[2-(3,4-dihydroxyphenyl)ethyl]amino]-4-oxobutanoic acid
• 英文别名: 4-[2-(3,4-Dihydroxyphenyl)ethylamino]-4-oxobutanoic acid
• CAS: 137476-48-3
• 化学式: C₁₂H₁₅NO₅
• 分子量: 253.255
• InChiKey: VBTFXBSNBWLHFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-amino-5-(aminomethyl)cyclohexylmethylamino-2-(2-furyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine trifluoroacetate 、 4-[[2-(3,4-dihydroxyphenyl)ethyl]amino]-4-oxobutanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到N1-((4-(((7-amino-2-(furan-2-yl)[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino)methyl)cyclohexyl)methyl)-N4-(3,4-dihydroxyphenethyl)succinamide
  参考文献：
  名称：

  A Novel Conjugated Agent between Dopamine and an A_2A Adenosine Receptor Antagonist as a Potential Anti-Parkinson Multitarget Approach

  摘要：

  We propose a potential antiparkinsonian prodrug DP-L-A(2A)ANT (2) obtained by amidic conjugation of dopamine (1) via a succinic spacer to a new triazolo-triazine A(2A) adenosine receptor (AR) antagonist A(2A)ANT (3). The affinity of 2 and its hydrolysis products-1, 3, dopamine-linker DP-L (4) and A(2A)ANT-linker L-A(2A)ANT (5)-was evaluated for hA(1), hA(2A), hA(2B) and hA(3) ARs and rat striatum A(2A)ARs or D-2 receptors. The hydrolysis patterns of 2, 4 and 5 and the stabilities of 1 and 3 were evaluated by HPLC analysis in human whole blood and rat brain homogenates. High hA(2A) affinity was shown by compounds 2 (K-i = 7.32 +/- 0.65 nM), 3 (K-i = 35 +/- 3 nM) and 5 (K-i = 72 +/- 5 nM), whose affinity values were similar in rat striatum. These compounds were not able to change dopamine affinity for D-2 receptors but counteracted the CGS 21680-induced reduction of dopamine affinity. DP-L (4) was inactive on adenosine and dopaminergic receptors. As for stability studies, compounds 4 and 5 were not degraded in incubation media. In human blood, the prodrug 2 was hydrolyzed (half-fife = 2.73 +/- 0.23 h) mainly on the amidic bound coupling the A(2A)ANT (3), whereas in rat brain homogenates the prodrug 2 was hydrolyzed (half-life > eight hours) exclusively on the amidic bound coupling dopamine, allowing its controlled release and increasing its poor stability as characterized by half-life = 22.5 +/- 1.5 min.

  DOI：

  10.1021/mp200489d
• 作为产物：
  描述：

  丁二酸酐 、 盐酸多巴胺 在 吡啶 作用下， 反应 12.0h， 以70%的产率得到4-[[2-(3,4-dihydroxyphenyl)ethyl]amino]-4-oxobutanoic acid
  参考文献：
  名称：

  A Novel Conjugated Agent between Dopamine and an A_2A Adenosine Receptor Antagonist as a Potential Anti-Parkinson Multitarget Approach

  摘要：

  We propose a potential antiparkinsonian prodrug DP-L-A(2A)ANT (2) obtained by amidic conjugation of dopamine (1) via a succinic spacer to a new triazolo-triazine A(2A) adenosine receptor (AR) antagonist A(2A)ANT (3). The affinity of 2 and its hydrolysis products-1, 3, dopamine-linker DP-L (4) and A(2A)ANT-linker L-A(2A)ANT (5)-was evaluated for hA(1), hA(2A), hA(2B) and hA(3) ARs and rat striatum A(2A)ARs or D-2 receptors. The hydrolysis patterns of 2, 4 and 5 and the stabilities of 1 and 3 were evaluated by HPLC analysis in human whole blood and rat brain homogenates. High hA(2A) affinity was shown by compounds 2 (K-i = 7.32 +/- 0.65 nM), 3 (K-i = 35 +/- 3 nM) and 5 (K-i = 72 +/- 5 nM), whose affinity values were similar in rat striatum. These compounds were not able to change dopamine affinity for D-2 receptors but counteracted the CGS 21680-induced reduction of dopamine affinity. DP-L (4) was inactive on adenosine and dopaminergic receptors. As for stability studies, compounds 4 and 5 were not degraded in incubation media. In human blood, the prodrug 2 was hydrolyzed (half-fife = 2.73 +/- 0.23 h) mainly on the amidic bound coupling the A(2A)ANT (3), whereas in rat brain homogenates the prodrug 2 was hydrolyzed (half-life > eight hours) exclusively on the amidic bound coupling dopamine, allowing its controlled release and increasing its poor stability as characterized by half-life = 22.5 +/- 1.5 min.

  DOI：

  10.1021/mp200489d

文献信息

• ANTITHROMBOTIC METALLIC MATERIAL
  申请人：Toray Industries, Inc.

  公开号：EP3278819A1

  公开（公告）日：2018-02-07

  The present invention aims to provide an antithrombogenic metallic material which is highly safe with its low hemolytic toxicity, and which continuously exhibits high antithrombogenicity. The present invention provides an antithrombogenic metallic material comprising a metallic material whose surface is coated with a coating material, the coating material containing: a phosphonic acid derivative or a catechol derivative; a polymer containing, as a constituent monomer, a compound selected from the group consisting of alkyleneimines, vinylamines, allylamines, lysine, protamine, and diallyldimethylammonium chloride; and an anionic compound containing a sulfur atom and having anticoagulant activity; the polymer being covalently bound to the phosphonic acid derivative or the catechol derivative, the phosphonic acid derivative or the catechol derivative being bound to the metallic material through a phosphonic acid group or a catechol group thereof, wherein the abundance ratio of nitrogen atoms to the abundance of total atoms as measured by X-ray photoelectron spectroscopy (XPS) on the surface is 4.0 to 13.0 atomic percent.

  本发明旨在提供一种抗血栓形成的金属材料，该材料具有低溶血性毒性，安全性高，并可持续表现出高抗血栓形成性。本发明提供了一种抗血栓形成金属材料，包括一种表面涂有涂层材料的金属材料，涂层材料含有一种膦酸衍生物或一种儿茶酚衍生物；一种聚合物，其组成单体是一种选自亚烷基亚胺、乙烯基胺、烯丙基胺、赖氨酸、原胺和二烯丙基二甲基氯化铵的化合物；以及一种含有硫原子并具有抗凝血活性的阴离子化合物；聚合物与膦酸衍生物或邻苯二酚衍生物共价结合，膦酸衍生物或邻苯二酚衍生物通过其膦酸基团或邻苯二酚基团与金属材料结合，其中表面上通过 X 射线光电子能谱（XPS）测量的氮原子丰度与总原子丰度之比为 4.0至13.0个原子百分点。
• COPOLYMER AND MEDICAL MATERIAL USING SAME
  申请人：Toray Industries, Inc.

  公开号：EP3521328A1

  公开（公告）日：2019-08-07

  The purpose of the present invention is to provide: a copolymer that is capable of being immobilized on a base material while maintaining a high antithrombotic property persistently without having to introduce heparin or an anticoagulant drug to the surface thereof; and a medical material using same. Provided is a copolymer that comprises monomer unit A, monomer unit B, and monomer unit C represented in in chemical formula 1, wherein monomer unit C has a mole fraction of 0.5-40% with respect to the total amount of all constituent monomer units.

  本发明的目的是提供一种共聚物，它能够固定在基底材料上，同时无需在其表面引入肝素或抗凝血药物就能持续保持较高的抗血栓性能；以及一种使用该共聚物的医用材料。本发明提供了一种共聚物，它由化学式 1 所表示的单体单元 A、单体单元 B 和单体单元 C 组成，其中单体单元 C 相对于所有组成单体单元总量的摩尔分数为 0.5-40%。
• COPOLYMER AND MEDICAL MATERIAL CONTAINING THE SAME
  申请人：Toray Industries, Inc.

  公开号：EP3845573A1

  公开（公告）日：2021-07-07

  The purpose of the present invention is to provide: a copolymer that is capable of being immobilized on a base material while maintaining a high antithrombotic property persistently without having to introduce heparin or an anticoagulant drug to the surface thereof; and a medical material using same. Provided is a copolymer that comprises monomer unit A, monomer unit B, and monomer unit C represented in in chemical formula 1, wherein monomer unit C has a mole fraction of 0.5-40% with respect to the total amount of all constituent monomer units.

  本发明的目的是提供一种共聚物，它能够固定在基底材料上，同时无需在其表面引入肝素或抗凝血药物就能持续保持较高的抗血栓性能；以及一种使用该共聚物的医用材料。本发明提供了一种共聚物，它由化学式 1 所表示的单体单元 A、单体单元 B 和单体单元 C 组成，其中单体单元 C 相对于所有组成单体单元总量的摩尔分数为 0.5-40%。
• Antithrombotic metallic material
  申请人：Toray Industries, Inc.

  公开号：US10709822B2

  公开（公告）日：2020-07-14

  An antithrombogenic metallic material includes a metallic material whose surface is coated with a coating material, the coating material containing: a phosphonic acid derivative or a catechol derivative; a polymer containing, as a constituent monomer, a compound selected from the group consisting of alkyleneimines, vinylamines, allylamines, lysine, protamine, and diallyldimethylammonium chloride; and an anionic compound containing a sulfur atom and having anticoagulant activity; the polymer being covalently bound to the phosphonic acid derivative or the catechol derivative, the phosphonic acid derivative or the catechol derivative being bound to the metallic material through a phosphonic acid group or a catechol group thereof, wherein the abundance ratio of nitrogen atoms to the abundance of total atoms as measured by X-ray photoelectron spectroscopy (XPS) on the surface is 4.0 to 13.0 atomic percent.

  一种抗血栓形成金属材料包括一种表面涂有涂层材料的金属材料，涂层材料包含一种膦酸衍生物或儿茶酚衍生物；一种聚合物，其组成单体是一种选自亚烷基亚胺、乙烯基胺、烯丙基胺、赖氨酸、原胺和二烯丙基二甲基氯化铵的化合物；以及一种含有硫原子并具有抗凝血活性的阴离子化合物；聚合物与膦酸衍生物或邻苯二酚衍生物共价结合，膦酸衍生物或邻苯二酚衍生物通过其膦酸基团或邻苯二酚基团与金属材料结合，其中表面上通过 X 射线光电子能谱（XPS）测量的氮原子丰度与总原子丰度之比为 4.0至13.0个原子百分点。
• Copolymer and medical material containing the same
  申请人：Toray Industries, Inc.

  公开号：US11000636B2

  公开（公告）日：2021-05-11

  A copolymer is capable of being immobilized on a base material while maintaining a high antithrombotic property persistently without having to introduce heparin or an anticoagulant drug to the surface thereof. The copolymer includes monomer unit A, monomer unit B, and monomer unit C, wherein monomer unit C has a mole fraction of 0.5-40% with respect to the total amount of all constituent monomer units.

  一种共聚物能够固定在基体材料上，同时能够持续保持较高的抗血栓性能，而无需在其表面引入肝素或抗凝血药物。该共聚物包括单体单元 A、单体单元 B 和单体单元 C，其中单体单元 C 相对于所有组成单体单元总量的摩尔分数为 0.5-40%。