methyl 1-hydroxy-5-phenyl-1H-indole-2-carboxylate | 1269802-95-0

• 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: methyl 1-hydroxy-5-phenyl-1H-indole-2-carboxylate
• 英文别名: Methyl 1-hydroxy-5-phenylindole-2-carboxylate
• CAS: 1269802-95-0
• 化学式: C₁₆H₁₃NO₃
• 分子量: 267.284
• InChiKey: PLPNOBZBLZQFFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 1-hydroxy-5-phenyl-1H-indole-2-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以90%的产率得到1-hydroxy-5-phenyl-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
• 作为产物：
  描述：

  3-甲基-4-硝基联苯 在 tin(II) chloride dihdyrate 、 sodium hydride 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 methyl 1-hydroxy-5-phenyl-1H-indole-2-carboxylate
  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

• 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.