1-(3',5'-dimethylphenyl)-3-(4-methyl-2-oxo-2H-chromen-7-yl)urea | 1366766-44-0

• 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: 1-(3',5'-dimethylphenyl)-3-(4-methyl-2-oxo-2H-chromen-7-yl)urea
• 英文别名: 1-(3,5-Dimethylphenyl)-3-(4-methyl-2-oxochromen-7-yl)urea
• CAS: 1366766-44-0
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: IPGFTURWEBMLSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7-氨基-4-甲基香豆素 、 3,5-二甲基苯基异氰酸酯 在 三乙胺 作用下， 以 丙酮 为溶剂， 反应 24.0h， 以23%的产率得到1-(3',5'-dimethylphenyl)-3-(4-methyl-2-oxo-2H-chromen-7-yl)urea
  参考文献：
  名称：

  [EN] CARBONIC ANHYDRASE INHIBITORS WITH ANTIMETASTATIC ACTIVITY
  [FR] INHIBITEURS D'ANHYDRASE CARBONIQUE PRÉSENTANT UNE ACTIVITÉ ANTIMÉTASTATIQUE

  摘要：

  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。

  公开号：

  WO2012070024A1

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。
• 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。
• CARBONIC ANHYDRASE IX-RELATED MARKERS AND USE THEREOF
  申请人：SignalChem Lifesciences Corporation

  公开号：EP2771488B1

  公开（公告）日：2018-03-28
• Novel coumarins and 2-thioxo-coumarins as inhibitors of the tumor-associated carbonic anhydrases IX and XII
  作者：Fabrizio Carta、Alfonso Maresca、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2012.02.014

  日期：2012.4

  A series of coumarins incorporating tert-butyl-dimethylsilyloxy- or allyoxy- moieties in positions 4-, 6 or 7 of the heterocyclic ring have been synthesized and then converted to the corresponding 2-thioxocoumarins. Other derivatives incorporating hydroxyethyloxy-, tosylethoxy- and 2-fluroethyloxy-moieties in position 7 of the coumarin ring were synthesized together with derivatives of 4-methyl-7-amino coumarin incorporating acetamido, 3,5-dimethylphenylureido- and tert-butyloxycarbonylamido functionalities. All these compounds were assayed as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The human (h) cytosolic isoforms hCA I and II were weakly inhibited (hCA I) or not inhibited at all (hCA II) by these (thioxo) coumarins whereas the tumor-associated transmembrane isoforms hCA IX and XII were inhibited with efficiencies from the submicromolar to the low micromolar range by many of these derivatives. The structure-activity relationship for these classes of less investigated CA inhibitors are delineated, with the potential of using them as leads to obtain isoform-selective inhibitors with excellent affinity for CA IX and XII (validated antitumor targets) which do not significantly inhibit the cytosolic offtarget isoforms hCA I and II. (C) 2012 Elsevier Ltd. All rights reserved.