(E)-3-(3,4-dihydroxyphenyl)-1-morpholinoprop-2-en-1-one | 100042-34-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3,4-dihydroxyphenyl)-1-morpholinoprop-2-en-1-one
• 英文别名: Kaffeesaeuremorpholid；4-[3-(3,4-dihydroxy-phenyl)-acryloyl]-morpholine；(E)-3-(3,4-dihydroxy-phenyl)-1-morpholin-4-yl-propenone；(E)-3-(3,4-dihydroxyphenyl)-1-morpholin-4-ylprop-2-en-1-one
• CAS: 100042-34-0
• 化学式: C₁₃H₁₅NO₄
• 分子量: 249.266
• InChiKey: QALAKMUXMRMKIZ-DUXPYHPUSA-N

物化性质

• 沸点：
  529.7±50.0 °C(Predicted)
• 密度：
  1.343±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(3,4-dihydroxyphenyl)-1-morpholinoprop-2-en-1-one 、 乙酸酐 在 硫酸 作用下， 生成 4-[3-(3,4-diacetoxy-phenyl)-acryloyl]-morpholine
  参考文献：
  名称：

  Flammang,M. et al., Chimica Therapeutica, 1969, vol. 4, p. 120 - 126

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4-二苄氧基苯甲醛 在 N-甲基吗啉 、 盐酸 、 potassium carbonate 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.17h， 生成 (E)-3-(3,4-dihydroxyphenyl)-1-morpholinoprop-2-en-1-one
  参考文献：
  名称：

  Tyrosinase inhibition and anti-melanin generation effect of cinnamamide analogues

  摘要：

  Abnormal melanogenesis results in excessive production of melanin, leading to pigmentation disorders. As a key and rate-limiting enzyme for melanogenesis, tyrosinase has been considered an important target for developing therapeutic agents of pigment disorders. Despite having an (E)-beta-phenyl-alpha,beta-unsaturated carbonyl scaffold, which plays an important role in the potent inhibition of tyrosinase activity, cinnamic acids have not attracted attention as potential tyrosinase inhibitors, due to their low tyrosinase inhibitory activity and relatively high hydrophilicity. Given that cinnamic acids' structure intrinsically features this (E)-scaffold and following our experience that minute changes in the chemical structure can powerfully affect tyrosinase activity, twenty less hydrophilic cinnamamide derivatives were designed as potential tyrosinase inhibitors and synthesised using a Horner-Wadsworth-Emmons reaction. Four of these cinnmamides (4, 9, 14, and 19) exhibited much stronger mushroom tyrosinase inhibition (over 90% inhibition) at 25 mu M compared to kojic acid (20.57% inhibition); crucially, all four have a 2,4-dihydroxy group on the beta-phenyl ring of the scaffold. A docking simulation using tyrosinase indicated that the four cinnamamides exceeded the binding affinity of kojic acid, and bound more strongly to the active site of tyrosinase. Based on the strength of their tyrosinase inhibition, these four cinnamamides were further evaluated in B16F10 melanoma cells. All four cinnamamides, without cytotoxicity, exhibited higher tyrosinase inhibitory activity (67.33 - 79.67% inhibition) at 25 mu M than kojic acid (38.11% inhibition), with the following increasing inhibitory order: morpholino (9) = cyclopentylamino (14) < cyclohexylamino (19) < N-methylpiperazino (4) cinnamamides. Analysis of tyrosinase activity and melanin content in B16F10 cells showed that the four cinnamamides dose-dependently inhibited both cellular tyrosinase activity and melanin content and that their inhibitory activity at 25 mu M was much better than that of kojic acid. The results of melanin content analysis well matched those of the cellular tyrosinase activity analysis, indicating that tyrosinase inhibition by the four cinnamamides is a major factor in the reduction of melanin production. These results imply that these four cinnamamides with a 2,4-dihydroxyphenyl group can act as excellent anti-melanogenic agents in the treatment of pigmentation disorders.

  DOI：

  10.1016/j.bioorg.2019.03.001

文献信息

• Synthesis and evaluation of caffeic acid amides as antioxidants
  作者：Padinchare Rajan、Irina Vedernikova、Paul Cos、Dirk Vanden Berghe、Koen Augustyns、Achiel Haemers

  DOI：10.1016/s0960-894x(00)00630-2

  日期：2001.1

  A series of amides of caffeic acid has been synthesised and their antioxidant properties evaluated as lipid peroxidation inhibitors. Anilides of caffeic acid were found to be very efficient antioxidants with IC50's of 0.3 microM.

  已经合成了一系列咖啡酸酰胺，并评估了它们的抗氧化性能作为脂质过氧化抑制剂。发现咖啡酸的苯甲酸酯是非常有效的抗氧化剂，IC50为0.3 microM。
• WO2008/26125
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury
  作者：Gaozhi Chen、Yali Zhang、Xing Liu、Qilu Fang、Zhe Wang、Lili Fu、Zhiguo Liu、Yi Wang、Yunjie Zhao、Xiaokun Li、Guang Liang

  DOI：10.1021/acs.jmedchem.5b01574

  日期：2016.3.24

  Acute inflammatory diseases, including acute lung injury and sepsis, remain the most common life-threatening illness in intensive care units worldwide. Cinnamamide has been incorporated in several synthetic compounds with therapeutic potentials including anti-inflammatory properties. However, the possible mechanism and direct molecular target of cinnamamides for their anti-inflammatory effects were rarely investigated. In this study, we synthesized a series of cinnamamides and evaluated their anti-inflammatory activities. The most active compound, 2i, was found to block LPS-induced MD2/TLR4 pro-inflammatory signaling activation in vitro and to attenuate LPS-caused sepsis and acute lung injury in vivo. Mechanistically, we demonstrated that 2i exerts its anti-inflammatory effects by directly targeting and binding MD2 in Arg90 and Tyr102 residues and inhibiting MD2/TLR4 complex formation. Taken together, this work presents a novel MD2 inhibitor, 2i, which has the potential to be developed as a candidate for the treatment of sepsis, and provides a new lead structure for the development of anti-inflammatory agents targeting MD2.
• [DE] AMIDE ZUR ERZEUGUNG EINES TRIGEMINALEN EFFEKTS<br/>[EN] AMIDES FOR GENERATING A TRIGEMINAL EFFECT<br/>[FR] AMIDE DESTINÉ À PRODUIRE UN EFFET TRIGÉMINAL
  申请人：SYMRISE AG

  公开号：WO2019063069A1

  公开（公告）日：2019-04-04

  Die vorliegende Erfindung betrifftdie Verwendung einer Verbindung der Formel (I) wie hierin beschriebenals Aromastoff. Die Erfindung betrifft zudem neue Verbindungender Formel (I) wie hierin beschrieben oder Mischungenumfassend eine oder mehrere unterschiedliche Verbindungen der Formel (I)wie hierin beschriebenoderbestehend aus mehreren unterschiedlichen Verbindungen der Formel (I)wie hierin beschrieben. Gemäß weiterer Aspekte betrifft die vorliegende Erfindung zudem Aromakompositionen umfassend oder bestehend aus einer Verbindung der Formel (I) wie hierin beschrieben oder Mischungen davon wie hierin beschrieben,pharmazeutische Zubereitungen, der Ernährung, der Mundhygiene oder dem Genuss dienende Zubereitungen, umfassend eine Verbindung der Formel (I) wie hierin beschrieben oder Mischungen davon wie hierin beschrieben oder Aromakompositionen wie hierin beschrieben,und Verfahren zum Herstellen einer pharmazeutischen Zubereitung, einer der Ernährung, der Mundhygiene oder dem Genuss dienenden Zubereitungwie hierin beschrieben.
• Flammang,M. et al., Chimica Therapeutica, 1969, vol. 4, p. 120 - 126
  作者：Flammang,M. et al.

  DOI：——

  日期：——