1-(4-羟基-3-甲氧基-5-硝基苯基)-2-苯基-乙酮 | 274925-97-2

• 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: 1-(4-羟基-3-甲氧基-5-硝基苯基)-2-苯基-乙酮
• 英文名称: BIA 3-270
• 英文别名: 1-(4-hydroxy-3-methoxy-5-nitrophenyl)-2-phenyl-ethanone；1-(4-hydroxy-3-methoxy-5-nitrophenyl)-2-phenyl-1-ethanone；1-(4-Hydroxy-3-methoxy-5-nitrophenyl)-2-phenylethanone
• CAS: 274925-97-2
• 化学式: C₁₅H₁₃NO₅
• 分子量: 287.272
• InChiKey: YXOCIHUZZWIPHW-UHFFFAOYSA-N

物化性质

• 熔点：
  129–130°C
• 沸点：
  429.2±40.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-羟基-3-甲氧基-5-硝基苯基)-2-苯基-乙酮 在 吡啶 、 三氯化铝 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以99.4%的产率得到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
• 作为产物：
  描述：

  1-(4-hydroxy-3-methoxyphenyl)-2-phenylethan-1-one 在 硝酸 、 溶剂黄146 作用下， 以60%的产率得到1-(4-羟基-3-甲氧基-5-硝基苯基)-2-苯基-乙酮
  参考文献：
  名称：

  Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-O-methyltransferase

  摘要：

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.

  DOI：

  10.1021/jm1001524

文献信息

• Synthesis of 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and Derivatives as Potent and Long-Acting Peripheral Inhibitors of Catechol-<i>O</i>-methyltransferase
  作者：David A. Learmonth、Maria A. Vieira-Coelho、Jan Benes、Paula C. Alves、Nuno Borges、Ana P. Freitas、Patrício Soares-da-Silva

  DOI：10.1021/jm0109964

  日期：2002.1.1

  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.
• 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 & Ca., S.A.

  公开号：EP1010688B1

  公开（公告）日：2003-04-09
• J. Med. Chem. 2002, 45, 685-695
  作者：

  DOI：——

  日期：——
• US6512136B1
  申请人：——

  公开号：US6512136B1

  公开（公告）日：2003-01-28
• Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-<i>O</i>-methyltransferase
  作者：László E. Kiss、Humberto S. Ferreira、Leonel Torrão、Maria João Bonifácio、P. Nuno Palma、Patrício Soares-da-Silva、David A. Learmonth

  DOI：10.1021/jm1001524

  日期：2010.4.22

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.