1-hydroxy-4-trifluoromethyl-1H-indole-2-carboxylic acid | 1269802-55-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-hydroxy-4-trifluoromethyl-1H-indole-2-carboxylic acid
• 英文别名: 1-hydroxy-4-trifluoromethyl-1H-indol-2-carboxylic acid；1-hydroxy-4-(trifluoromethyl)indole-2-carboxylic acid
• CAS: 1269802-55-2
• 化学式: C₁₀H₆F₃NO₃
• 分子量: 245.158
• InChiKey: VHZRBRJSTLLOSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  62.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-甲基-3-硝基三氟甲苯 在 tin(II) chloride dihdyrate 、 sodium hydride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 1-hydroxy-4-trifluoromethyl-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Discovery of N-Hydroxyindole-Based Inhibitors of Human Lactate Dehydrogenase Isoform A (LDH-A) as Starvation Agents against Cancer Cells

  摘要：

  Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from "normal" oxidative phosphorylation to increased glycolysis even under. sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate dehydrogenase (LDH-A), is overexpressed by metastatic cancer cells and is linked to the vitality of tumors in hypoxia. This enzyme may be considered as a potential target for new anticancer agents, since its inhibition cuts cancer energetic and anabolic supply, thus reducing the metastatic and invasive potential of cancer cells. We have discovered new and efficient N-hydroxyindole-based inhibitors of LDH-A, which are isoform-selective (over LDH-B) and competitive with both the substrate (pyruvate) and the cofactor (NADH). The antiproliferative activity of these compounds was confirmed on a series of cancer cell lines, and they proved to be particularly effective under hypoxic conditions. Moreover, NMR experiments showed that these compounds are able to reduce the glucose-to-lactate conversion inside the cell.

  DOI：

  10.1021/jm101007q

文献信息

• [EN] COMPOUNDS INHIBITORS OF ENZYME LACTATE DEHYDROGENASE (LDH) AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'ENZYME LACTATE DÉSHYDROGÉNASE (LDH) ET COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSÉS
  申请人：UNIV PISA

  公开号：WO2011054525A1

  公开（公告）日：2011-05-12

  The present invention concerns compounds, some of which are novel, and their pharmaceutical applications. The compounds of the invention inhibit the enzyme lactate dehydrogenase (LDH) involved both in the metabolic process of hypoxic tumour cells, and in the process used by parasitic protozoa that cause malaria to obtain most of the energy they need.

  这项发明涉及化合物，其中一些是新颖的，以及它们的药用应用。该发明的化合物抑制乳酸脱氢酶（LDH）酶，该酶参与低氧肿瘤细胞的代谢过程，以及疟疾引起的寄生原虫利用获取所需大部分能量的过程。
• COMPOUNDS INHIBITORS OF ENZYME LACTATE DEHYDROGENASE (LDH) AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS
  申请人：Universita Di Pisa

  公开号：EP2499114A1

  公开（公告）日：2012-09-19
• Discovery of <i>N</i>-Hydroxyindole-Based Inhibitors of Human Lactate Dehydrogenase Isoform A (LDH-A) as Starvation Agents against Cancer Cells
  作者：Carlotta Granchi、Sarabindu Roy、Chiara Giacomelli、Marco Macchia、Tiziano Tuccinardi、Adriano Martinelli、Mario Lanza、Laura Betti、Gino Giannaccini、Antonio Lucacchini、Nicola Funel、Leticia G. León、Elisa Giovannetti、Godefridus J. Peters、Rahul Palchaudhuri、Emilia C. Calvaresi、Paul J. Hergenrother、Filippo Minutolo

  DOI：10.1021/jm101007q

  日期：2011.3.24

  Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from "normal" oxidative phosphorylation to increased glycolysis even under. sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate dehydrogenase (LDH-A), is overexpressed by metastatic cancer cells and is linked to the vitality of tumors in hypoxia. This enzyme may be considered as a potential target for new anticancer agents, since its inhibition cuts cancer energetic and anabolic supply, thus reducing the metastatic and invasive potential of cancer cells. We have discovered new and efficient N-hydroxyindole-based inhibitors of LDH-A, which are isoform-selective (over LDH-B) and competitive with both the substrate (pyruvate) and the cofactor (NADH). The antiproliferative activity of these compounds was confirmed on a series of cancer cell lines, and they proved to be particularly effective under hypoxic conditions. Moreover, NMR experiments showed that these compounds are able to reduce the glucose-to-lactate conversion inside the cell.