3-硝基-5-苯基乙酰基邻苯二酚 | 274925-86-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 3-硝基-5-苯基乙酰基邻苯二酚
• 中文别名: 5,6-二甲基苯并呋喃；硝苄卡朋
• 英文名称: Nebicapone
• 英文别名: 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone；BIA 3-202；1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-1-ethanone；1-[3,4-dihydroxy-5-nitrophenyl]-2-phenyl-ethanone；1-[3,4-dihydroxy-5-nitrophenyl]-2-phenylethanone；1-(3,4-dihydroxy-5-nitrophenyl)-2-phenylethanone
• CAS: 274925-86-9
• 化学式: C₁₄H₁₁NO₅
• 分子量: 273.245
• InChiKey: MRFOLGFFTUGAEB-UHFFFAOYSA-N

物化性质

• 熔点：
  178–179°C
• 沸点：
  454.2±45.0 °C(Predicted)
• 密度：
  1.435±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  -20°C，干燥且密封保存。

制备方法与用途

生物活性

Nebicapone（BIA 3-202）是一种可逆的儿茶酚-O-甲基转移酶（COMT）抑制剂，主要通过葡萄糖醛酸化代谢。作为一种外周作用为主的抑制剂，Nebicapone 通过抑制 COMT 减少 L-DOPA 向 3-O-甲基-DOPA 的生物转化。因此，Nebicapone 可用于帕金森病的研究。

反应信息

• 作为反应物：
  描述：

  3-硝基-5-苯基乙酰基邻苯二酚 在 吡啶 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以34%的产率得到1-(3,4-dihydroxy-5-nitrophenyl)-1-hydroxyimino-2-phenyl-ethane
  参考文献：
  名称：

  Synthesis of 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and Derivatives as Potent and Long-Acting Peripheral Inhibitors of Catechol-O-methyltransferase

  摘要：

  A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration). The effects of structural modifications to 7b on COMT inhibitory profile were investigated, and it is concluded that the carbonyl group and preferably unsubstituted aromatic ring are essential features to maintain prolonged peripheral COMT inhibition. The introduction of the alpha-methylene group, the major structural difference between 7b and 1, would appear responsible for the observed enhancement in selectivity of peripheral COMT inhibition of 7b, which has more limited access to the brain than 1.

  DOI：

  10.1021/jm0109964
• 作为产物：
  描述：

  4-苄氧基-3-甲氧基苯甲醛 在 吡啶 、 三氯化铝 、 sodium dichromate 、 硫酸 、 四丁基溴化铵 、 氢溴酸 、 硝酸 、 magnesium 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 3-硝基-5-苯基乙酰基邻苯二酚
  参考文献：
  名称：

  IMPROVED METHOD FOR DEMETHYLATION OF NITRO- CATECHOL METHYL ETHERS

  摘要：

  Several nitro-catechol compounds. useful as inhibitors of COMT were obtained in excellent yield and purity via an improved procedure for demethylation of the corresponding methyl ethers using aluminium chloride and pyridine in ethyl acetate.

  DOI：

  10.1081/scc-120002413

文献信息

• Substituted 2-phenyl-1-(3,4-dihydroxy-5-nitrophenyl)-1-ethanones, their use in the treatment of some central and peripheral nervous system disorders and pharmaceutical compositions containing them
  申请人：Portela & C.A., S.A.

  公开号：US06512136B1

  公开（公告）日：2003-01-28

  New compounds of formula I are described The compounds have potentially valuable pharmaceutical properties in the treatment of some central and peripheral nervous system disorders, where a reduction in the O-methylation of catecholamines may be of therapeutical benefit, such as Parkinson's disease and parkinsonian disorders, gastrointestinal disturbances, edema formation states and hypertension.

  公式I的新化合物被描述。这些化合物在治疗某些中枢和外周神经系统疾病中具有潜在的有价值的药理特性，其中对儿茶酚胺的O-甲基化减少可能具有治疗效果，比如帕金森病和帕金森综合征、胃肠道紊乱、水肿和高血压。
• Pharmaceutical compositions comprising droxidopa
  申请人：Chelsea Therapeutics, Inc.

  公开号：EP2363123A1

  公开（公告）日：2011-09-07

  The present invention provides combinations of droxidopa and one or more further pharmaceutically active compounds, said further compounds preferentially being selected from the group of COMT inhibiting compounds, cholinesterase inhibiting compounds, and monoamine oxidase inhibiting compounds. The invention further provides methods of treating conditions, such as orthostatic hypotension, comprising administering the combinations.

  本发明提供了屈昔多巴和一种或多种进一步的药学活性化合物的组合物，所述进一步的化合物优选选自COMT抑制化合物、胆碱酯酶抑制化合物和单胺氧化酶抑制化合物组。本发明进一步提供了治疗诸如直立性低血压等病症的方法，包括施用这些组合物。
• Droxidopa and pharmaceutical composition thereof for the treatment of fibromyalgia
  申请人：Chelsea Therapeutics, Inc.

  公开号：EP2468271A1

  公开（公告）日：2012-06-27

  The present invention provides methods of treating fibromyalgia or other diseases or conditions causing widespread pain and/or fatigue. In particular, the invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active agents, that can be used in the inventive methods. The methods of treatment can comprise treating, preventing, reducing, or eliminating a variety of symptoms recognized as indicative of fibromyalgia, such as chronic pain, allodynia, hyperalgesia, fatigue, sleep disturbance, and depression.

  本发明提供了治疗纤维肌痛或其他引起广泛疼痛和/或疲劳的疾病或病症的方法。特别是，本发明提供了可用于本发明方法的包含单独或与一种或多种其他活性剂组合的屈昔多巴的药物组合物。治疗方法可包括治疗、预防、减轻或消除各种公认的纤维肌痛症状，如慢性疼痛、异痛症、痛觉减退、疲劳、睡眠障碍和抑郁。
• Droxidopa and pharmaceutical composition thereof for the treatment of mood disorders, sleep disorders, or attention deficit disorders
  申请人：Chelsea Therapeutics, Inc.

  公开号：EP2514417A2

  公开（公告）日：2012-10-24

  The present invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active ingredients, for the treatment of conditions, such as mood disorders, sleep disorders, or attention deficit disorders. In certain embodiments, the compositions useful in the methods of the invention comprise droxidopa and a compound selected from the group consisting of DOPA decarboxylase inhibiting compounds, catechol-O-methyltransferase inhibiting compounds, cholinesterase inhibiting compounds, monoamine oxidase inhibiting compounds, norepinephrine reuptake inhibiting compounds, selective serotonin reuptake inhibiting compounds, tricyclic antidepressant compounds, serotonin norepinephrine reuptake inhibiting compounds, norepinephrine dopamine reuptake inhibiting compound, noradrenergic and specific serotonergic antidepressants, and combinations thereof. The inventive compositions are particularly useful in the treatment of depression, narcolepsy, insomnia, and Attention Deficit/Hyperactivity Disorder (AD/HD).

  本发明提供了包含单独或与一种或多种其他活性成分组合的屈昔多巴的药物组合物，用于治疗情绪障碍、睡眠障碍或注意力缺陷障碍等疾病。在某些实施方案中，用于本发明方法的组合物包含屈昔多巴和一种选自由 DOPA 脱羧酶抑制化合物、儿茶酚-O-甲基转移酶抑制化合物、胆碱酯酶抑制化合物、单胺氧化酶抑制化合物组成的组的化合物、去甲肾上腺素再摄取抑制化合物、选择性血清素再摄取抑制化合物、三环类抗抑郁剂化合物、血清素去甲肾上腺素再摄取抑制化合物、去甲肾上腺素多巴胺再摄取抑制化合物、去甲肾上腺素能和特异性血清素能抗抑郁剂，以及它们的组合。本发明组合物尤其适用于治疗抑郁症、嗜睡症、失眠症和注意力缺陷/多动症（AD/HD）。
• Metalloenzyme inhibitors using metal binding moieties in combination with targeting moieties
  申请人：Viamet Pharmaceuticals, Inc.

  公开号：EP2543368A1

  公开（公告）日：2013-01-09

  The presently disclosed subject matter is described to metalloenzyme inhibitors having metal binding moieties linked to a targeting moiety through a linking group or a direct bond, method of screening for metalloenzyme inhibitors, and methods for treating a metalloenzyme related disorder by administering a metalloenzyme inhibitor to a subject in need of treatment thereof.

  目前公开的主题涉及金属酶抑制剂，其金属结合分子通过连接基团或直接键与靶向分子相连；金属酶抑制剂的筛选方法；以及通过向需要治疗的受试者施用金属酶抑制剂来治疗金属酶相关疾病的方法。