2-methoxy-3-(phenylamino)naphthalene-1,4-dione | 69009-67-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-methoxy-3-(phenylamino)naphthalene-1,4-dione
• 英文别名: 2-anilino-3-methoxynaphthalene-1,4-dione
• CAS: 69009-67-2
• 化学式: C₁₇H₁₃NO₃
• 分子量: 279.295
• InChiKey: IDALHZBWBHNQOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 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：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3-二氯-1,4-萘醌 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 12.5h， 生成 2-methoxy-3-(phenylamino)naphthalene-1,4-dione
  参考文献：
  名称：

  Discovery of Novel 2-Aniline-1,4-naphthoquinones as Potential New Drug Treatment for Leber’s Hereditary Optic Neuropathy (LHON)

  摘要：

  Leber's hereditary optic neuropathy (LHON) is a rare genetic mitochondrial disease and the primary cause of chronic visual impairment for at least 1 in 10 000 individuals in the U.K. Treatment options remain limited, with only a few drug candidates and therapeutic approaches, either approved or in development. Recently, idebenone has been investigated as drug therapy in the treatment of LHON, although evidence for the efficacy of idebenone is limited in the literature. NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III were identified as the major enzymes involved in idebenone activity. Based on this mode of action, computer-aided techniques and structure-activity relationship (SAR) optimization studies led to the discovery of a series naphthoquinone-related small molecules, with comparable adenosine 5'-triphosphate (ATP) rescue activity to idebenone. Among these, three compounds showed activity in the nanomolar range and one, 2-((4-fluoro-3-(trifluoromethyl)phenyl)amino)-3-(methylthio)naphthalene-1,3-dione (1), demonstrated significantly higher potency ex vivo, and significantly lower cytotoxicity, than idebenone.

  DOI：

  10.1021/acs.jmedchem.0c00942

文献信息

• INHIBITORS OF THE MITF MOLECULAR PATHWAY
  申请人：THE GENERAL HOSPITAL CORPORATION

  公开号：US20160130222A1

  公开（公告）日：2016-05-12

  Provided herein are compounds of the formula (IV) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful as MITF inhibitors, MITF pathway inhibitors and for the treatment of cancer.

  本文提供的是公式（IV）的化合物及其药学上可接受的盐，其中取代基如规范中所披露的那样。这些化合物及其含有的药物组合物可用作MITF抑制剂、MITF通路抑制剂以及治疗癌症的药物。
• [EN] INHIBITORS OF THE MITF MOLECULAR PATHWAY<br/>[FR] INHIBITEURS DE LA VOIE MOLÉCULAIRE MITF
  申请人：GEN HOSPITAL CORP

  公开号：WO2014201016A3

  公开（公告）日：2015-02-05
• BIOMARKERS PREDICTIVE OF CANCER CELL RESPONSE TO ML329 OR A DERIVATIVE THEREOF
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20220128562A1

  公开（公告）日：2022-04-28

  The present invention is based in part on the identification of biomarkers, including NQO1, NRF2 and KEAP1, predictive of cancer cell responsiveness to treatment with ML 329 or a derivative thereof.
• US9745261B2
  申请人：——

  公开号：US9745261B2

  公开（公告）日：2017-08-29
• Discovery of Novel 2-Aniline-1,4-naphthoquinones as Potential New Drug Treatment for Leber’s Hereditary Optic Neuropathy (LHON)
  作者：Carmine Varricchio、Kathy Beirne、Pascale Aeschlimann、Charles Heard、Malgorzata Rozanowska、Marcela Votruba、Andrea Brancale

  DOI：10.1021/acs.jmedchem.0c00942

  日期：2020.11.25

  Leber's hereditary optic neuropathy (LHON) is a rare genetic mitochondrial disease and the primary cause of chronic visual impairment for at least 1 in 10 000 individuals in the U.K. Treatment options remain limited, with only a few drug candidates and therapeutic approaches, either approved or in development. Recently, idebenone has been investigated as drug therapy in the treatment of LHON, although evidence for the efficacy of idebenone is limited in the literature. NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III were identified as the major enzymes involved in idebenone activity. Based on this mode of action, computer-aided techniques and structure-activity relationship (SAR) optimization studies led to the discovery of a series naphthoquinone-related small molecules, with comparable adenosine 5'-triphosphate (ATP) rescue activity to idebenone. Among these, three compounds showed activity in the nanomolar range and one, 2-((4-fluoro-3-(trifluoromethyl)phenyl)amino)-3-(methylthio)naphthalene-1,3-dione (1), demonstrated significantly higher potency ex vivo, and significantly lower cytotoxicity, than idebenone.