6-(benzo[d][1,3]dioxol-5-yl)-1-hydroxy-1H-indole-2-carboxylic acid | 1303571-81-4

• 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: 6-(benzo[d][1,3]dioxol-5-yl)-1-hydroxy-1H-indole-2-carboxylic acid
• 英文别名: 6-(1,3-Benzodioxol-5-yl)-1-hydroxyindole-2-carboxylic acid
• CAS: 1303571-81-4
• 化学式: C₁₆H₁₁NO₅
• 分子量: 297.267
• InChiKey: GWLMJYDHCHDICI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  80.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-甲基-3-硝基苯硼酸 在 tin(II) chloride dihdyrate 、 四丁基溴化铵 、 palladium diacetate 、 sodium hydride 、 sodium carbonate 、 苯硫酚 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 0.16h， 生成 6-(benzo[d][1,3]dioxol-5-yl)-1-hydroxy-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  N-Hydroxyindole-based inhibitors of lactate dehydrogenase against cancer cell proliferation

  摘要：

  Current cancer research is being increasingly focused on the study of distinctive characters of tumour metabolism, resulting in a switch from oxidative phosphorylation to glycolysis (Warburg effect). Isoform 5 of human lactate dehydrogenase (hLDH5), which catalyzes the final step in the glycolytic cascade (pyruvate to lactate), constitutes a relatively new and untapped anti-cancer target. In this study, careful design and synthesis of a selected series of aryl-substituted N-hydroxyindole-2-carboxylates (NHIs) has led to several hLDH5-inhibitors, showing "first-in-class" potency and isoform selectivity. Enzyme kinetics studies indicated that these inhibitors exhibit a competitive mode of inhibition. Some representative examples were tested against two human pancreatic carcinoma cell lines, and displayed a good antiproliferative activity, which was even more evident under hypoxic conditions. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.046

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
• LDH INHIBITORS AS TREATMENT FOR FIBROSIS AND FIBROTIC-RELATED DISORDERS
  申请人：Kottmann Robert M.

  公开号：US20150335674A1

  公开（公告）日：2015-11-26

  One aspect of the disclosure relates to methods of treating a fibrotic condition in an individual. The methods include administering to an individual having a fibrotic condition an effective amount of a lactic dehydrogenase (LDH) inhibitor, wherein the fibrotic condition involves an internal organ or tissue, or ocular tissue, and said administering is effective to treat the fibrotic condition. Methods of administration and pharmaceutical compositions and systems for practicing such methods are also disclosed.
• US9750761B2
  申请人：——

  公开号：US9750761B2

  公开（公告）日：2017-09-05
• N-Hydroxyindole-based inhibitors of lactate dehydrogenase against cancer cell proliferation
  作者：Carlotta Granchi、Sarabindu Roy、Alessio De Simone、Irene Salvetti、Tiziano Tuccinardi、Adriano Martinelli、Marco Macchia、Mario Lanza、Laura Betti、Gino Giannaccini、Antonio Lucacchini、Elisa Giovannetti、Rocco Sciarrillo、Godefridus J. Peters、Filippo Minutolo

  DOI：10.1016/j.ejmech.2011.08.046

  日期：2011.11

  Current cancer research is being increasingly focused on the study of distinctive characters of tumour metabolism, resulting in a switch from oxidative phosphorylation to glycolysis (Warburg effect). Isoform 5 of human lactate dehydrogenase (hLDH5), which catalyzes the final step in the glycolytic cascade (pyruvate to lactate), constitutes a relatively new and untapped anti-cancer target. In this study, careful design and synthesis of a selected series of aryl-substituted N-hydroxyindole-2-carboxylates (NHIs) has led to several hLDH5-inhibitors, showing "first-in-class" potency and isoform selectivity. Enzyme kinetics studies indicated that these inhibitors exhibit a competitive mode of inhibition. Some representative examples were tested against two human pancreatic carcinoma cell lines, and displayed a good antiproliferative activity, which was even more evident under hypoxic conditions. (C) 2011 Elsevier Masson SAS. All rights reserved.