(E)-phenethyl 3-(2,5-dihydroxyphenyl)acrylate

• 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)-phenethyl 3-(2,5-dihydroxyphenyl)acrylate
• 英文别名: phenethyl (E)-3-(2,5-dihydroxyphenyl)prop-2-enoate；2-phenylethyl (E)-3-(2,5-dihydroxyphenyl)prop-2-enoate
• 化学式: C₁₇H₁₆O₄
• 分子量: 284.312
• InChiKey: OQKRMXDGEFRBAJ-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-phenethyl 3-(2,5-dihydroxyphenyl)acrylate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以92%的产率得到3-(2,5-dihydroxyphenyl)propanoic acid β-phenylethyl ester
  参考文献：
  名称：

  细胞蛋白通过埃布斯汀和相关化合物的交联。

  摘要：

  蛋白质-酪氨酸激酶抑制剂和稳定的厄布他汀类似物2,5-二羟基肉桂酸甲酯（4）通过非生理化学机理交联细胞蛋白质（Stanwell等，Cancer Res 55：4950-4956，1995）。为了确定这种作用的结构要求，合成了埃布斯汀（1）和15种相关化合物，包括咖啡酸苯乙基酯（9），并研究了它们在低微摩尔至最高1000浓度范围内诱导细胞蛋白交联的能力。 microM。测试在NIH3T3成纤维细胞以及小鼠角质形成细胞中进行。在低至10-50 microM的浓度下，许多类似物（包括埃布他汀）均观察到细胞蛋白的有效交联。与相应的二羟基化对应物相比，甲氧基和氟的惰性表明游离的芳族羟基对于交联是必不可少的。另外，含有具有1，4-二羟基取代基的苯环的化合物比具有1，2-二羟基化图案的那些化合物更有效。与原型化合物4一样，在37度和4度都诱导了交联，表明是化学机制而非生理机制。与数据一致，提出了一种作用

  DOI：

  10.1016/0006-2952(96)00250-x
• 作为产物：
  描述：

  氯-乙酸苯乙酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 180.0h， 生成 (E)-phenethyl 3-(2,5-dihydroxyphenyl)acrylate
  参考文献：
  名称：

  发现一种新型的基于2,5-二羟基肉桂酸的5-脂氧合酶抑制剂，该抑制剂诱导细胞凋亡并可能损害RCC4肾癌细胞中的自噬通量

  摘要：

  近年来，抑制白三烯（LTs）生物合成的关键酶5-脂氧合酶（5-LO）引起了越来越高的热情，成为抗炎和抗肿瘤的策略。根据我们以前的研究，我们合成了一系列可能是5-LO抑制剂的基于二羟基肉桂酸的类似物。测量了LT在HEK293细胞和多形核白细胞（PMNL）中的生物合成抑制作用，并在肾细胞癌（RCC）中研究了其抗肿瘤活性。结果表明，2,5-二羟基肉桂酸苯乙酯（10b）是最好的5-LO抑制剂，并且其效力是唯一被临床批准的5-LO抑制剂Zileuton（1）的7倍。由于化合物10b， 2，5-二羟基取代更有利于5-LO抑制其活性是作为3，4-二羟基肉桂酸酯的CAPE（2）的两倍。同时，10b降低了肾癌细胞的细胞生存力，并且对缺乏Von Hippel-Lindau（VHL）肿瘤抑制基因的RCC4和786.0细胞更具选择性。至于潜在的细胞死亡机制，10b诱导VHL缺失的RCC4细胞凋亡。此外，LC3B和

  DOI：

  10.1016/j.ejmech.2019.06.060

文献信息

• Synthesis and characterization of CAPE derivatives as xanthine oxidase inhibitors with radical scavenging properties
  作者：Wonbeen Choi、Valente Villegas、Hannah Istre、Ben Heppler、Niki Gonzalez、Nicole Brusman、Lindsey Snider、Emily Hogle、Janelle Tucker、Alma Oñate、Sandra Oñate、Lili Ma、Stefan Paula

  DOI：10.1016/j.bioorg.2019.02.049

  日期：2019.5

  of the enzyme xanthine oxidase (XO) with radical scavenging properties hold promise as novel agents against reperfusion injuries after ischemic events. By suppressing the formation of damaging reactive oxygen species (ROS) by XO or scavenging ROS from other sources, these compounds may prevent a buildup of ROS in the aftermath of a heart attack or stroke. To combine these two properties in a single molecule

  具有自由基清除特性的黄嘌呤氧化酶（XO）酶抑制剂有望作为抵抗缺血事件后再灌注损伤的新型药物。通过抑制XO破坏性活性氧（ROS）的形成或从其他来源清除ROS，这些化合物可预防心脏病发作或中风后ROS的积聚。为了在单个分子中结合这两个特性，我们使用方便的微波辅助Knoevenagel缩合方案合成并表征了非嘌呤XO抑制剂咖啡酸苯乙酯（CAPE）和19种衍生物。系统地改变两个苯环上羟基的数量和位置，我们基于实验确定的XO抑制数据得出了结构活性关系。分子对接表明，关键的酶/抑制剂相互作用涉及酚类抑制剂环与Tyr914之间的π-π相互作用，抑制剂羟基与Glu802之间的氢键以及CAPE苯环与位于肽入口的非极性残基之间的疏水相互作用。结合位点。为了有效清除稳定的自由基DPPH，在苯环的1,2-或1,4-位需要两个羟基。在所有测试的化合物中，E-苯基3-（3,4-二羟基苯基）丙烯酸酯（一种不带乙基醚的CA
• Hydroxylated Aromatic Inhibitors of HIV-1 Integrase
  作者：Terrence R. Jr. Burke、Mark Fesen、Abhijit Mazumder、Jessie Yung、Jian Wang、Adelaide M. Carothers、Dezider Grunberger、John Driscoll、Yves Pommier、Kurt Kohn

  DOI：10.1021/jm00021a006

  日期：1995.10

  Efficient replication of HIV-1 requires integration of a DNA copy of the viral genome into a chromosome of the host cell. Integration is catalyzed by the viral integrase, and we have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAFE, 2), and curcumin confer inhibitory activity against HIV-1 integrase. We now extend these findings by performing a comprehensive structure-activity relationship using CAPE analogues. Approximately 30 compounds have been prepared as HIV integrase inhibitors based on the structural lead provided by CAPE, which has previously been shown to exhibit an IC50 value of 7 mu M in our integration assay. These analogues were designed to examine specific features of the parent CAFE structure which may be important for activity. Among the features examined for their effects on inhibitory potency were ring substitution, side chain length and composition, and phenyl ring conformational orientation. In an assay which measured the combined effect of two sequential steps, dinucleotide cleavage and strand transfer, several analogues have IC50 values for 3'-processing and strand transfer lower than those of CAFE. Inhibition of strand transfer was assayed using both blunt-ended and ''precleaved'' DNA substrates. Disintegration using an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA-binding domains was also inhibited by these analogues, suggesting that the binding site for these compounds resides in the central catalytic core. Several CAFE analogues were also tested for selective activity against transformed cells. Taken together, these results suggest that the development of novel antiviral agents for the treatment of acquired immune deficiency syndrome can be based upon inhibition of HIV-1 integrase.
• A METHOD FOR THE TREATMENT OF HYPERPROLIFERATIVE EPITHELIAL SKIN DISEASES BY TOPICAL APPLICATION OF HYDROXYLATED AROMATIC PROTEIN CROSS-LINKING COMPOUNDS
  申请人：THE UNITED STATES GOVERNMENT as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：EP0809493A1

  公开（公告）日：1997-12-03
• METHODS OF TREATING SKIN DISORDERS WITH CAFFEIC ACID ANALOGS
  申请人：CONRAD CHARLES

  公开号：US20080167277A1

  公开（公告）日：2008-07-10

  Methods of treating skin diseases such as plaque psoriasis and inverse psoriasis include topical application of one or a combination of caffeic acid phenethyl ester, caffeic acid benzyl ester, and analogs thereof as an active agent. A pharmaceutical composition containing the active agent may further include a cell differentiating agent such as a retinoid, and/or vitamin D or analogs thereof. The method enables treatment of a lesion with active agent dosages of ten percent by weight, for example.
• US5610185A
  申请人：——

  公开号：US5610185A

  公开（公告）日：1997-03-11