2-oxo-7-((4-(trifluoromethyl)benzyl)oxy)-2H-chromene-3-carboxylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2-oxo-7-((4-(trifluoromethyl)benzyl)oxy)-2H-chromene-3-carboxylic acid
• 英文别名: 2-Oxo-7-[[4-(trifluoromethyl)phenyl]methoxy]chromene-3-carboxylic acid；2-oxo-7-[[4-(trifluoromethyl)phenyl]methoxy]chromene-3-carboxylic acid
• 化学式: C₁₈H₁₁F₃O₅
• 分子量: 364.278
• InChiKey: NNMCQEWPXADCQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-oxo-7-((4-(trifluoromethyl)benzyl)oxy)-2H-chromene-3-carboxylic acid 、 1-(2-aminoethyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one 在 4-二甲氨基吡啶 、 2-巯基噻唑啉 、 N,N'-二环己基碳二亚胺 、 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 以95.2%的产率得到N-(2-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl)-2-oxo-7-((4-(trifluoromethyl)benzyl)oxy)-2H-chromene-3-carboxamide
  参考文献：
  名称：

  具潜在抗AD活性的香豆素杂合吡啶酮酰胺衍 生物及其制备方法与应用

  摘要：

  本发明公开了一种香豆素杂合吡啶酮酰胺衍生物及其制备方法与应用。所述的香豆素杂合吡啶酮酰胺衍生物及其药学上可接受的盐如式(I)或式(II)所示，其可应用于制备抗阿尔兹海默症、抗帕金森病或通过抑制单胺氧化酶、螯合金属铁离子、抗Aβ及抗氧化来治疗的其它疾病或病症药物方面的用途。

  公开号：

  CN110804045B
• 作为产物：
  描述：

  7-羟基香豆素-3-羧酸乙酯 在 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.25h， 生成 2-oxo-7-((4-(trifluoromethyl)benzyl)oxy)-2H-chromene-3-carboxylic acid
  参考文献：
  名称：

  Rational design, synthesis and biological evaluation of novel multitargeting anti-AD iron chelators with potent MAO-B inhibitory and antioxidant activity

  摘要：

  A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multi targeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe(3+) values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC50 value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid-beta(1-42) (A beta(1-42)) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.

  DOI：

  10.1016/j.bmc.2020.115550

文献信息

• 具潜在抗AD活性的香豆素杂合吡啶酮酰胺衍 生物及其制备方法与应用
  申请人：浙江工业大学

  公开号：CN110804045B

  公开（公告）日：2021-07-27

  本发明公开了一种香豆素杂合吡啶酮酰胺衍生物及其制备方法与应用。所述的香豆素杂合吡啶酮酰胺衍生物及其药学上可接受的盐如式(I)或式(II)所示，其可应用于制备抗阿尔兹海默症、抗帕金森病或通过抑制单胺氧化酶、螯合金属铁离子、抗Aβ及抗氧化来治疗的其它疾病或病症药物方面的用途。
• [EN] 3-CARBOXY SUBSTITUTED COUMARIN DERIVATIVES WITH A POTENTIAL UTILITY FOR THE TREATMENT OF CANCER DISEASES<br/>[FR] DÉRIVÉS DE COUMARINE 3-CARBOXY SUBSTITUÉS PRÉSENTANT UNE UTILITÉ POTENTIELLE DANS LE TRAITEMENT DES MALADIES CANCÉREUSES
  申请人：UNIV CATHOLIQUE LOUVAIN

  公开号：WO2014195507A1

  公开（公告）日：2014-12-11

  The present invention relates to novel compounds. The present invention also relates to the compounds for use as a medicine, more in particular for the prevention or treatment of cancer, more in particular cancers expressing MCT1 and/or MCT4. The present invention also relates to a method for the prevention or treatment of cancer in animals or humans by using the novel compounds. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds and to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of cancer. The present invention also relates to processes for the preparation of the compounds.

  本发明涉及新化合物。本发明还涉及用作药物的化合物，更具体地用于预防或治疗癌症，更具体地是表达MCT1和/或MCT4的癌症。本发明还涉及一种通过使用新化合物预防或治疗动物或人类癌症的方法。本发明还涉及新化合物的药物组合物或联合制剂，以及用作药物的组合物或制剂，更优选地用于预防或治疗癌症。本发明还涉及制备这些化合物的方法。
• 3-CARBOXY SUBSTITUTED COUMARIN DERIVATIVES WITH A POTENTIAL UTILITY FOR THE TREATMENT OF CANCER DISEASES
  申请人：UNIVERSITE CATHOLIQUE DE LOUVAIN

  公开号：US20160115146A1

  公开（公告）日：2016-04-28

  The present invention relates to novel compounds. The present invention also relates to the compounds for use as a medicine, more in particular for the prevention or treatment of cancer, more in particular cancers expressing MCT1 and/or MCT4. The present invention also relates to a method for the prevention or treatment of cancer in animals or humans by using the novel compounds. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds and to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of cancer. The present invention also relates to processes for the preparation of the compounds.

  本发明涉及新颖化合物。本发明还涉及用于药物的化合物，更具体地用于预防或治疗癌症，更具体地用于表达MCT1和/或MCT4的癌症。本发明还涉及使用新颖化合物预防或治疗动物或人类癌症的方法。本发明还涉及新颖化合物的制药组合物或复方制剂，以及用于药物的组合物或制剂，更优选用于预防或治疗癌症。本发明还涉及制备这些化合物的方法。
• Rational design, synthesis and biological evaluation of novel multitargeting anti-AD iron chelators with potent MAO-B inhibitory and antioxidant activity
  作者：Xiaoying Jiang、Jianan Guo、Yangjing Lv、Chuansheng Yao、Changjun Zhang、Zhisheng Mi、Yuan Shi、Jinping Gu、Tao Zhou、Renren Bai、Yuanyuan Xie

  DOI：10.1016/j.bmc.2020.115550

  日期：2020.6

  A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multi targeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe(3+) values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC50 value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid-beta(1-42) (A beta(1-42)) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.