7-((3-fluorobenzyl)oxy)-2-oxo-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: 7-((3-fluorobenzyl)oxy)-2-oxo-2H-chromene-3-carboxylic acid
• 英文别名: 7-[(3-Fluorophenyl)methoxy]-2-oxochromene-3-carboxylic acid；7-[(3-fluorophenyl)methoxy]-2-oxochromene-3-carboxylic acid
• 化学式: C₁₇H₁₁FO₅
• 分子量: 314.27
• InChiKey: FNUMDBQBXKRCOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-((3-fluorobenzyl)oxy)-2-oxo-2H-chromene-3-carboxylic acid 在 氯化亚砜 作用下， 生成
  参考文献：
  名称：

  带有色胺的香豆素-3-羧酰胺的合成及其抗胆碱酯酶活性

  摘要：

  许多ñ - （2-（1- ħ吲哚-3-基）乙基）-2-氧代- 2 ħ色烯-3-甲酰胺的合成和对乙酰胆碱酯酶和丁酰胆碱酯酶测试。合成化合物4a-o的体外评估表明，它们中的大多数对AChE具有显着活性。SAR研究表明，在香豆素支架的7位上引入苄氧基部分可以提高抗AChE活性。在化合物4o的情况下，使用7-（4-氟苄基）氧基部分可获得最佳结果，IC 50值为0.16μM。根据AChE的对接研究，原型化合物4o 在整个活性位点上均被覆盖，并同时占据了周围的阴离子位点（PAS）和催化的阴离子位点（CAS）。

  DOI：

  10.1016/j.ejmech.2016.05.014
• 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 N,N-二甲基甲酰胺 为溶剂， 生成 7-((3-fluorobenzyl)oxy)-2-oxo-2H-chromene-3-carboxylic acid
  参考文献：
  名称：

  带有色胺的香豆素-3-羧酰胺的合成及其抗胆碱酯酶活性

  摘要：

  许多ñ - （2-（1- ħ吲哚-3-基）乙基）-2-氧代- 2 ħ色烯-3-甲酰胺的合成和对乙酰胆碱酯酶和丁酰胆碱酯酶测试。合成化合物4a-o的体外评估表明，它们中的大多数对AChE具有显着活性。SAR研究表明，在香豆素支架的7位上引入苄氧基部分可以提高抗AChE活性。在化合物4o的情况下，使用7-（4-氟苄基）氧基部分可获得最佳结果，IC 50值为0.16μM。根据AChE的对接研究，原型化合物4o 在整个活性位点上均被覆盖，并同时占据了周围的阴离子位点（PAS）和催化的阴离子位点（CAS）。

  DOI：

  10.1016/j.ejmech.2016.05.014

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。
• Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents
  作者：Tooba Abdizadeh、Mohammad Reza Kalani、Khalil Abnous、Zahra Tayarani-Najaran、Bibi Zahra Khashyarmanesh、Rahman Abdizadeh、Razieh Ghodsi、Farzin Hadizadeh

  DOI：10.1016/j.ejmech.2017.03.024

  日期：2017.5

  synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec). We evaluated their inhibitory activities against pan HDAC and HDAC1 isoform. Four compounds (8f, 8q, 8r and 8u) showed significant cytotoxicity with IC50 in the range of 0.53-57

  组蛋白脱乙酰基酶（HDAC）是治疗癌症和其他疾病的有吸引力的治疗靶标。它具有四类（I-IV），其中特别是I类同工酶与促进肿瘤细胞的增殖，血管生成，分化，侵袭和转移有关，并且也是癌症治疗的可行靶标。设计并合成了一系列新的基于香豆素的苯甲酰胺作为HDAC抑制剂。评估了合成的化合物（8a-u）对六种人类癌细胞系的细胞毒活性，包括HCT116，A2780，MCF7，PC3，HL60和A549，以及一种正常细胞系（Huvec）。我们评估了它们对泛HDAC和HDAC1亚型的抑制活性。四种化合物（8f，8q，8r和8u）显示出明显的细胞毒性，IC50在0.53-57范围内。47±0.02μM几乎等于参比药物恩替司他（IC50 = 0.41±0.06μM）。化合物8a的分子对接研究和分子动力学模拟显示了该化合物与HDAC1酶之间可能的相互作用方式。47±0.02μM几乎等于参比药物恩替司他（IC50 = 0
• 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。
• Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells
  作者：Nihed Draoui、Olivier Schicke、Antony Fernandes、Xavier Drozak、Fady Nahra、Amélie Dumont、Jonathan Douxfils、Emmanuel Hermans、Jean-Michel Dogné、Romu Corbau、Arnaud Marchand、Patrick Chaltin、Pierre Sonveaux、Olivier Feron、Olivier Riant

  DOI：10.1016/j.bmc.2013.09.010

  日期：2013.11

  Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential therapeutic targets to limit cancer progression. In this study, we have developed and implemented a stepwise in vitro screening procedure on human cancer cells to identify new potent MCT inhibitors. Various 7-substituted carboxycoumarins and quinolinone derivatives were synthesized and pharmacologically evaluated. Most active compounds were obtained using a palladium-catalyzed Buchwald-Hartwig type coupling reaction, which proved to be a quick and efficient method to obtain aminocarboxycoumarin derivatives. Inhibition of lactate flux revealed that the most active compound 19 (IC50 11 nM) was three log orders more active than the CHC reference compound. Comparison with warfarin, a conventional anticoagulant coumarin, further showed that compound 19 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux. (C) 2013 Elsevier Ltd. All rights reserved.