2-amino-3-(4-fluorophenyl)-1,4-naphthoquinone | 327099-01-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-amino-3-(4-fluorophenyl)-1,4-naphthoquinone
• 英文别名: 2-Amino-3-(4-fluorophenyl)naphthalene-1,4-dione
• CAS: 327099-01-4
• 化学式: C₁₆H₁₀FNO₂
• 分子量: 267.259
• InChiKey: WDAGWOWSJZSZJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-1,4-萘醌 在 palladium diacetate 、 N-碘吗啉氢碘酸盐 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 生成 2-amino-3-(4-fluorophenyl)-1,4-naphthoquinone
  参考文献：
  名称：

  P2X7 receptor inhibition by 2-amino-3-aryl-1,4-naphthoquinones

  摘要：

  Extracellular ATP activates purinergic receptors such as P2X7, cationic channels for Ca2+, K+, and Na+. There is robust evidence of the involvement of these receptors in the immune response, so P2X7 receptors (P2X7R) are considered a potential therapeutic target for the development of anti-inflammatory drugs. Although there are many studies of the anti-inflammatory properties of naphthoquinones, these molecules have not yet been explored as P2X7 antagonists. In previous work, our group prepared 3-substituted (halogen or aryl) 2-hydroxy-1,4-naphthoquinones and studied their action on P2X7R. In this paper, eight 2-amino-3-aryl-1,4-naphthoquinones were evaluated to identify the inhibitory activity on P2X7R and the toxicological profile. Three analogues (AD-4CN, AD-4Me, and AD-4F) exhibited reduced toxicity for mammalian cells with CC50 values higher than 500 mu M. These three 3-substituted 2-amino-1,4-naphthoquinones inhibited murine P2X7R (mP2X7R) in vitro. However, the analogues AD-4CN and AD-4Me showed low selectivity index values. AD-4F inhibited both mP2X7R and human P2X7R (hP2X7R) with IC50 values of 0.123 and 0.93 mu M, respectively. Additionally, this analogue exhibited higher potency than BBG at inhibiting the ATP-induced release of IL-1 beta in vitro. Carrageenaninduced paw edema in vivo was reversed for AD-4F with an ID50 value of 11.51 ng/kg. Although AD-4F was less potent than previous 3-substituted (halogen or aryl) 2-hydroxy-1,4-naphthoquinones such as AN-04 in vitro, this 3-substituted 2-amino-1,4-naphthoquinone revealed higher potency in vivo to reduce the edematogenic response. In silico analysis suggests that the binding site of the novel 2-amino-3-aryl-1,4-naphthoquinone derivatives, including all the tautomeric forms, is located in the pore area of the hP2X7R model. Based on these results, we considered AD-4F to be a satisfactory P2X7R inhibitor. AD-4F might be used as a scaffold structure to design a novel series of inhibitors with potential inhibitory activity on murine (mP2X7R) and human (hP2X7R) P2X7 receptors.

  DOI：

  10.1016/j.bioorg.2020.104278

文献信息

• Aryl-Free Radical-Mediated Oxidative Arylation of Naphthoquinones Using <i>o</i>-Iodoxybenzoic Acid and Phenylhydrazines and Its Application toward the Synthesis of Benzocarbazoledione
  作者：Pravin Patil、Abhay Nimonkar、Krishnacharya G. Akamanchi

  DOI：10.1021/jo500131h

  日期：2014.3.7

  Oxidative arylation of naphthoquinones has been developed through combination of o-iodoxybenzoic acid with arylhydrazines under mild conditions at open atmosphere. Arylated naphthoquinones with different electronic properties were obtained in moderate to good yields. The postulated radical mediated mechanism is supported by radical trapping experiments. Developed protocol for direct arylation of naphthoquinones has been extended toward short, high yielding, and an effective synthesis of antitumor-antibiotic precursor such as benzocarbazoledione.
• P2X7 receptor inhibition by 2-amino-3-aryl-1,4-naphthoquinones
  作者：Daniela de Luna Martins、Adriel Alves Borges、Nayane A. do A. e Silva、Juliana Vieira Faria、Lucas Villas Bôas Hoelz、Hellen Valério Chaves Moura de Souza、Murilo Lamim Bello、Nubia Boechat、Vitor Francisco Ferreira、Robson Xavier Faria

  DOI：10.1016/j.bioorg.2020.104278

  日期：2020.11

  Extracellular ATP activates purinergic receptors such as P2X7, cationic channels for Ca2+, K+, and Na+. There is robust evidence of the involvement of these receptors in the immune response, so P2X7 receptors (P2X7R) are considered a potential therapeutic target for the development of anti-inflammatory drugs. Although there are many studies of the anti-inflammatory properties of naphthoquinones, these molecules have not yet been explored as P2X7 antagonists. In previous work, our group prepared 3-substituted (halogen or aryl) 2-hydroxy-1,4-naphthoquinones and studied their action on P2X7R. In this paper, eight 2-amino-3-aryl-1,4-naphthoquinones were evaluated to identify the inhibitory activity on P2X7R and the toxicological profile. Three analogues (AD-4CN, AD-4Me, and AD-4F) exhibited reduced toxicity for mammalian cells with CC50 values higher than 500 mu M. These three 3-substituted 2-amino-1,4-naphthoquinones inhibited murine P2X7R (mP2X7R) in vitro. However, the analogues AD-4CN and AD-4Me showed low selectivity index values. AD-4F inhibited both mP2X7R and human P2X7R (hP2X7R) with IC50 values of 0.123 and 0.93 mu M, respectively. Additionally, this analogue exhibited higher potency than BBG at inhibiting the ATP-induced release of IL-1 beta in vitro. Carrageenaninduced paw edema in vivo was reversed for AD-4F with an ID50 value of 11.51 ng/kg. Although AD-4F was less potent than previous 3-substituted (halogen or aryl) 2-hydroxy-1,4-naphthoquinones such as AN-04 in vitro, this 3-substituted 2-amino-1,4-naphthoquinone revealed higher potency in vivo to reduce the edematogenic response. In silico analysis suggests that the binding site of the novel 2-amino-3-aryl-1,4-naphthoquinone derivatives, including all the tautomeric forms, is located in the pore area of the hP2X7R model. Based on these results, we considered AD-4F to be a satisfactory P2X7R inhibitor. AD-4F might be used as a scaffold structure to design a novel series of inhibitors with potential inhibitory activity on murine (mP2X7R) and human (hP2X7R) P2X7 receptors.