7-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]-2H-chromen-2-one | 1379521-08-0

• 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-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]-2H-chromen-2-one
• 英文别名: 7-(1-phenyl-1H-[1,2,3]triazol-4-ylmethoxy)-chromen-2-one；4-(7-coumarinoxymethyl)-1-phenyl-1H-1,2,3-triazole；7-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one；7-[(1-Phenyltriazol-4-yl)methoxy]chromen-2-one；7-[(1-phenyltriazol-4-yl)methoxy]chromen-2-one
• CAS: 1379521-08-0
• 化学式: C₁₈H₁₃N₃O₃
• 分子量: 319.32
• InChiKey: LZILEQYIQFONPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯胺 在 盐酸 、 四甲基氯化铵 、 sodium nitrite 作用下， 以 水 、 叔丁醇 为溶剂， 反应 6.0h， 生成 7-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]-2H-chromen-2-one
  参考文献：
  名称：

  Click-tailed coumarins with potent and selective inhibitory action against the tumor-associated carbonic anhydrases IX and XII

  摘要：

  Coumarins behave as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) with a mechanism of inhibition distinct from other classes of inhibitors. A series of 7-substituted coumarins incorporating aryl-triazole moieties were prepared by click chemistry procedures starting from 7-hydroxycoumarin or 4-methyl-7-aminocoumarin. The panel of new compounds was assayed for the inhibition of the cytosolic, widespread human (h) isoforms hCA I and II, and the transmembrane, tumor-associated ones hCA IX and XII. Most of the coumarins were weak inhibitors or did not inhibit significantly hCA I and II, but showed low nanomolar inhibitory action against the transmembrane isoforms (K-I of 14.3-34.4 nM against hCA IX and of 4.7-37.8 nM against hCA XII). Since many hypoxic tumors over-express hCA IX/XII, and as these targets were recently validated for obtaining antitumor/antimetastatic agents, with one inhibitor in Phase I clinical trials, the present findings constitute an interesting extension to the knowledge of non-sulfonamide, selective inhibitors of CA isoforms involved in serious pathologies. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.041

文献信息

• [EN] CARBONIC ANHYDRASE INHIBITORS WITH ANTIMETASTATIC ACTIVITY<br/>[FR] INHIBITEURS D'ANHYDRASE CARBONIQUE PRÉSENTANT UNE ACTIVITÉ ANTIMÉTASTATIQUE
  申请人：METASIGNAL THERAPEUTICS INC

  公开号：WO2012070024A1

  公开（公告）日：2012-05-31

  Compositions for the treatment of cancer comprising coumarin and thiocoumarin derivatives of Formulas I- XII are disclosed. Said derivatives preferentially inhibit carbonic anhydrase IX and XII (which are associated with hypoxic and metastatic tumours) over inhibiting carbonic anhydrase I and II activity. The compositions therefore are suited for treatment of hypoxic or metastatic cancers due to this selective mechanism of action.

  本发明揭示了用于治疗癌症的组合物，包括公开的具有I-XII式的香豆素和硫代香豆素衍生物。所述衍生物优先抑制与低氧和转移性肿瘤相关的碳酸酐酶IX和XII，而不是抑制碳酸酐酶I和II的活性。因此，这些组合物由于这种选择性作用机制而适用于治疗低氧或转移性癌症。
• Thioxocoumarins Show an Alternative Carbonic Anhydrase Inhibition Mechanism Compared to Coumarins
  作者：Marta Ferraroni、Fabrizio Carta、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1021/acs.jmedchem.5b01720

  日期：2016.1.14

  A series of coumarins and the corresponding 2-thioxocoumarines were prepared and tested for their inhibition profiles against four physiologically relevant human carbonic anhydrases (hCAs, EC 4.2.1.1), isoforms hCA I, II, IX, and XII. The X-ray crystal structure of 6-hydroxy-2-thioxocoumarin bound to hCA II revealed an unprecedented and unexpected inhibition mechanism for this new class of inhibitors

  制备了一系列香豆素和相应的2-硫代香豆素，并测试了它们对四种生理相关的人碳酸酐酶（hCAs，EC 4.2.1.1），同工型hCA I，II，IX和XII的抑制作用。与同型香豆素相比，与hCA II结合的6-羟基-2-硫代香豆素的X射线晶体结构揭示了这种新型抑制剂的前所未有的，出乎意料的抑制机制。与香豆素通过酯酶CA活性水解成相应的2-羟基肉桂酸衍生物不同，与hCA II结合时，观察到2-thioxo香豆素是完整的，其外切-硫原子锚定在锌配位的水分子上，而支架与活性位点的氨基酸残基建立了良好的接触。这种抑制机理与观察到的水解香豆素的阻滞机理非常不同，水解香豆素阻塞了活性部位腔的入口。香豆素/硫氧还香豆素结合模式的这种多功能性对设计同工型选择性CA抑制剂具有重要意义，其中某些抑制剂在临床上或临床上用于各种病理，包括青光眼，水肿，癫痫，神经性疼痛和低氧肿瘤。
• Highly Efficient Ultrasonic-Assisted CuCl-Catalyzed 1,3-Dipolar Cycloaddition Reactions in Water: Synthesis of Coumarin Derivatives Linked with 1,2,3-Triazole Moiety
  作者：Xu Li、Xiaolan Chen、Yuqin Jiang、Senshen Chen、Lingbo Qu、Zhibo Qu、Jinwei Yuan、Hanyu Shi

  DOI：10.1002/jhet.2175

  日期：2016.9

  By introducing ultrasound irradiation into “on water” CuCl‐catalyzed 1,3‐dipolar Huisgen cycloaddition, the reaction efficiencies were notably promoted toward a wide variety of applicable azides and alkynes at room temperature, and a series of coumarin derivatives linked with 1,2,3‐triazole moiety were synthesized using the optimized conditions.

  通过将超声波辐射引入“水上” CuCl催化的1,3-偶极Huisgen环加成反应中，在室温下，对于多种适用的叠氮化物和炔烃，以及一系列与1,2连接的香豆素衍生物，反应效率得到了显着提高。在优化的条件下合成了3-3-三唑部分。
• CARBONIC ANHYDRASE INHIBITORS WITH ANTIMETASTATIC ACTIVITY
  申请人：Supuran Claudiu

  公开号：US20140148400A1

  公开（公告）日：2014-05-29

  Derivatized coumarin-based pharmaceutical compositions and methods to use them are provided. The compositions are characterized in that they inhibit the activity of tumor-related CAIX and CAXII to a greater degree than they inhibit the activity of CAI and CAII. The compositions can be used to suppress tumor growth and/or suppress tumor metastases in a mammal.

  提供了衍生香豆素类制药组合物及其使用方法。这些组合物的特征在于它们抑制肿瘤相关的CAIX和CAXII的活性，而不是CAI和CAII的活性。这些组合物可用于抑制哺乳动物中的肿瘤生长和/或抑制肿瘤转移。
• Click-tailed coumarins with potent and selective inhibitory action against the tumor-associated carbonic anhydrases IX and XII
  作者：Alessio Nocentini、Fabrizio Carta、Mariangela Ceruso、Gianluca Bartolucci、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2015.09.041

  日期：2015.11

  Coumarins behave as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) with a mechanism of inhibition distinct from other classes of inhibitors. A series of 7-substituted coumarins incorporating aryl-triazole moieties were prepared by click chemistry procedures starting from 7-hydroxycoumarin or 4-methyl-7-aminocoumarin. The panel of new compounds was assayed for the inhibition of the cytosolic, widespread human (h) isoforms hCA I and II, and the transmembrane, tumor-associated ones hCA IX and XII. Most of the coumarins were weak inhibitors or did not inhibit significantly hCA I and II, but showed low nanomolar inhibitory action against the transmembrane isoforms (K-I of 14.3-34.4 nM against hCA IX and of 4.7-37.8 nM against hCA XII). Since many hypoxic tumors over-express hCA IX/XII, and as these targets were recently validated for obtaining antitumor/antimetastatic agents, with one inhibitor in Phase I clinical trials, the present findings constitute an interesting extension to the knowledge of non-sulfonamide, selective inhibitors of CA isoforms involved in serious pathologies. (C) 2015 Elsevier Ltd. All rights reserved.