1-(4-hydroxy-3-methoxyphenyl)-3-phenylpropan-1-one | 709030-19-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 1-(4-hydroxy-3-methoxyphenyl)-3-phenylpropan-1-one
• 英文别名: 1-(4-hydroxy-3-methoxy-phenyl)-3-phenyl-propan-1-one；1-(4-Hydroxy-3-methoxy-phenyl)-3-phenyl-propan-1-on；4'-Hydroxy-3'-methoxy-3-phenylpropiophenon；Benzyl acetovanillone
• CAS: 709030-19-3
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: IKODPFSNRZMCNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-hydroxy-3-methoxyphenyl)-3-phenylpropan-1-one 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 乙酸酐 、 copper(II) nitrate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-(4-Hydroxy-3-methoxy-2-nitro-phenyl)-3-phenyl-propan-1-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Novel Series of “Ortho-Nitrated” Inhibitors of Catechol-O-methyltransferase

  摘要：

  Novel regioisomeric "ortho-nitrated" catechols related to the catechol-O-methyltransferase (COMT) inhibitors BIA 3-202 3 and BIA 3-335 4 were synthesized and biologically evaluated. Changing the position of the nitro group from the "classical" meta- to the ortho-position relative to the side-chain substituent of the nitrocatechol pharmacophore exerted profound effects on selectivity and duration of COMT inhibition. Alkylaryl compounds 7a-d possessed shorter duration of action than their regioisomers, but 7b displayed reversed selectivity over 3 at 3 and 6 h, exhibiting preferential central inhibition. In the amino-substituted series, ortho-nitrated regioisomer 14k was less peripherally selective than 4 and short-acting, whereas decahydroquinoline 14g displayed an unprecedented combination of long-acting and selective peripheral inhibition. 7b could provide a useful tool to probe the pharmacological utility of short-acting, centrally selective COMT inhibitors in the treatment of depression in Parkinsonian patients, and 14g represents a promising candidate for clinical evaluation as an adjunct to L-Dopa therapy.

  DOI：

  10.1021/jm0580454
• 作为产物：
  描述：

  (E)-3-(2-bromophenyl)-1-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以100%的产率得到1-(4-hydroxy-3-methoxyphenyl)-3-phenylpropan-1-one
  参考文献：
  名称：

  噻唑衍生物在体外和体内作为环氧合酶抑制剂。

  摘要：

  环氧合酶（COXs）是重要的膜结合血红素酶，对血小板活化和炎症很重要。COX-1在大多数细胞中组成性表达，而COX-2是在炎症条件下高表达的诱导型亚型。已经进行了研究以评价噻唑衍生物作为抗炎分子。在这项研究中，我们研究了两种新型噻唑衍生物化合物1（N- [4-（4-羟基-3-甲氧基苯基）-1,3-噻唑-2-基]乙酰胺）和化合物的体外和体内作用2（4-（2-氨基-1,3-噻唑-4-基）-2-甲氧基苯酚）对炎症环境中前列腺素E2（PGE2）的产生和COX活性的影响。我们的结果表明，化合物1（IC50 9.01±0.01µM）和化合物2（IC50 11.65±6.20µM）（Mean±SEM）对COX-2依赖性PGE2的产生均具有有效抑制作用。我们还确定了COX-1活性是否被抑制。使用稳定过量表达COX-1和人血小板的细胞，我们显示化合物1是具有CO50（5.56×10（-8）±2.26×10（-8）µM）的COX-1特异性抑制剂。

  DOI：

  10.1016/j.ejphar.2015.01.008

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.
• v. Wacek; Kratzl, Chemische Berichte, 1944, vol. 77/79, p. 516,519
  作者：v. Wacek、Kratzl

  DOI：——

  日期：——
• Synthesis and Biological Evaluation of a Novel Series of “Ortho-Nitrated” Inhibitors of Catechol-<i>O</i>-methyltransferase
  作者：David A. Learmonth、Maria João Bonifácio、Patrício Soares-da-Silva

  DOI：10.1021/jm0580454

  日期：2005.12.1

  Novel regioisomeric "ortho-nitrated" catechols related to the catechol-O-methyltransferase (COMT) inhibitors BIA 3-202 3 and BIA 3-335 4 were synthesized and biologically evaluated. Changing the position of the nitro group from the "classical" meta- to the ortho-position relative to the side-chain substituent of the nitrocatechol pharmacophore exerted profound effects on selectivity and duration of COMT inhibition. Alkylaryl compounds 7a-d possessed shorter duration of action than their regioisomers, but 7b displayed reversed selectivity over 3 at 3 and 6 h, exhibiting preferential central inhibition. In the amino-substituted series, ortho-nitrated regioisomer 14k was less peripherally selective than 4 and short-acting, whereas decahydroquinoline 14g displayed an unprecedented combination of long-acting and selective peripheral inhibition. 7b could provide a useful tool to probe the pharmacological utility of short-acting, centrally selective COMT inhibitors in the treatment of depression in Parkinsonian patients, and 14g represents a promising candidate for clinical evaluation as an adjunct to L-Dopa therapy.
• Thiazole derivatives as inhibitors of cyclooxygenases in vitro and in vivo
  作者：Ghewa A. El-Achkar、Mariam Jouni、May F. Mrad、Taghreed Hirz、Nehme El Hachem、Ali Khalaf、Soukaina Hammoud、Hussein Fayyad-Kazan、Assaad A. Eid、Bassam Badran、Raghida Abou Merhi、Ali Hachem、Eva Hamade、Aïda Habib

  DOI：10.1016/j.ejphar.2015.01.008

  日期：2015.3

  and in vivo effects of two novel thiazole derivatives compound 1 (N-[4-(4-hydroxy-3-methoxyphenyl)-1,3-thiazol-2-yl] acetamide) and compound 2 (4-(2-amino-1,3-thiazol-4-yl)-2-methoxyphenol) on prostaglandin E2 (PGE2) production and COX activity in inflammatory settings. Our results reveal a potent inhibition of both compound 1 (IC50 9.01±0.01µM) and 2 (IC50 11.65±6.20µM) (Mean±S.E.M.) on COX-2-dependent

  环氧合酶（COXs）是重要的膜结合血红素酶，对血小板活化和炎症很重要。COX-1在大多数细胞中组成性表达，而COX-2是在炎症条件下高表达的诱导型亚型。已经进行了研究以评价噻唑衍生物作为抗炎分子。在这项研究中，我们研究了两种新型噻唑衍生物化合物1（N- [4-（4-羟基-3-甲氧基苯基）-1,3-噻唑-2-基]乙酰胺）和化合物的体外和体内作用2（4-（2-氨基-1,3-噻唑-4-基）-2-甲氧基苯酚）对炎症环境中前列腺素E2（PGE2）的产生和COX活性的影响。我们的结果表明，化合物1（IC50 9.01±0.01µM）和化合物2（IC50 11.65±6.20µM）（Mean±SEM）对COX-2依赖性PGE2的产生均具有有效抑制作用。我们还确定了COX-1活性是否被抑制。使用稳定过量表达COX-1和人血小板的细胞，我们显示化合物1是具有CO50（5.56×10（-8）±2.26×10（-8）µM）的COX-1特异性抑制剂。