2-chloro-3-((3-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione | 143586-69-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-chloro-3-((3-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione
• 英文别名: 1,4-Naphthalenedione, 2-chloro-3-[[3-(trifluoromethyl)phenyl]amino]-；2-chloro-3-[3-(trifluoromethyl)anilino]naphthalene-1,4-dione
• CAS: 143586-69-0
• 化学式: C₁₇H₉ClF₃NO₂
• 分子量: 351.712
• InChiKey: FSTVLAQUGNREID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  丙烷-1-硫醇 、 2-chloro-3-((3-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 以69%的产率得到2-(isopropylthio)-3-((3-(trifluoromethyl)phenyl)amino)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
• 作为产物：
  描述：

  2,3-二氯-1,4-萘醌 、 间氨基三氟甲苯 以 乙醇 为溶剂， 以66%的产率得到2-chloro-3-((3-(trifluoromethyl)phenyl)amino)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

• 2,3-Disubstituted-1,4-naphthoquinones containing an arylamine with trifluoromethyl group: synthesis, biological evaluation, and computational study
  作者：Hatice Yıldırım、Nilüfer Bayrak、Amac Fatih Tuyun、Emel Mataracı Kara、Berna Özbek Çelik、Girish Kumar Gupta

  DOI：10.1039/c7ra00868f

  日期：——

  This study deals with the synthesis, characterization of structures, in silico PASS prediction, and the discovery of antibacterial and antifungal properties based on new sulfanyl-1,4-naphthoquinone derivatives containing an arylamine with a trifluoromethyl group at different positions, which can be further applied in drug discovery and development. The in vitro antimicrobial potential of the newly synthesized

  抗菌和抗真菌有机化合物在生物医学应用中变得越来越重要。这项研究涉及结构的合成，结构表征，计算机PASS预测，以及基于在不同位置含有三氟甲基芳基胺的新硫烷基-1,4-萘醌衍生物的发现，发现其抗菌和抗真菌特性，这可能是进一步的研究。在药物发现和开发中的应用。在体外的新合成的化合物的抗微生物潜力在七个细菌菌株（3革兰氏阳性和四个革兰氏阴性细菌）和一种酵母一个面板进行评价，对抗生物膜活性的额外的研究。化合物（5b和5e）被鉴定为对人源性病原体表皮葡萄球菌具有很强的抗菌作用，抑制浓度值极低（分别为4.88和2.44μgmL -1）。详细研究了这两种化合物（5b和5e）的毒性，以将这些化合物与头孢呋辛（一种临床证明的药物）进行比较。化合物5f的抗菌活性等于头孢呋辛。此外，三种化合物（5b，5e和5f）表现出优异的抗菌活性，而5b和5e其活性分别是参比抗微生物化合物（头孢呋辛）的两倍和四倍。因此，这三种
• 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.