2-oxo-7-(pyrrolidin-1-yl)-2H-chromene-3-carboxylic acid | 1448314-01-9

• 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-(pyrrolidin-1-yl)-2H-chromene-3-carboxylic acid
• 英文别名: 2-Oxo-7-pyrrolidin-1-ylchromene-3-carboxylic acid；2-oxo-7-pyrrolidin-1-ylchromene-3-carboxylic acid
• CAS: 1448314-01-9
• 化学式: C₁₄H₁₃NO₄
• 分子量: 259.262
• InChiKey: AZGXIHFVKOMJRL-UHFFFAOYSA-N

物化性质

• 沸点：
  504.7±50.0 °C(predicted)
• 密度：
  1.425±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(1-吡咯烷)苯酚 在 哌啶 、 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 2-oxo-7-(pyrrolidin-1-yl)-2H-chromene-3-carboxylic acid
  参考文献：
  名称：

  香豆素羧酸作为单羧酸转运蛋白 1 抑制剂：作为潜在抗癌药物的体外和体内研究

  摘要：

  通过抑制单羧酸转运蛋白 1 (MCT1)，合成了新型N , N-二烷基羧基香豆素作为潜在的抗癌剂。这些香豆素羧酸的体外 MCT1 抑制、MTT 癌细胞活力、双向 Caco-2 细胞通透性以及在人类和肝微粒体中的稳定性已得到评估。这些结果表明，主要候选化合物之一4a具有良好的吸收、代谢稳定性和较低的药物流出率。在健康小鼠中对先导化合物4a进行的全身毒性研究表明，与对照组相比，该抑制剂具有良好的耐受性，动物死亡率为零，体重增加正常。小鼠体内肿瘤生长抑制研究表明，候选化合物4a在表达MCT1的GL261-luc2同种移植模型中表现出显着的单药活性，但在表达MCT4的MDA-MB-231异种移植模型中没有表现出显着的活性，表明4a的选择性对于表达 MCT1 的肿瘤。

  DOI：

  10.1016/j.bmcl.2016.05.054

文献信息

• [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。
• 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.
• THERAPEUTIC COMPOUNDS
  申请人：Regents of the University of Minnesota

  公开号：US20140371272A1

  公开（公告）日：2014-12-18

  The invention provides compounds of formula (I) or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula (I) and therapeutic methods for treating cancer or treating autoimmune diseases or preventing transplant rejection using compounds of formula (I).
• US9296728B2
  申请人：——

  公开号：US9296728B2

  公开（公告）日：2016-03-29