N-(2-phenylethyl)-4-hydroxycinnamamide | 103197-54-2

• 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: N-(2-phenylethyl)-4-hydroxycinnamamide
• 英文别名: (E)-3-(4-hydroxyphenyl)-N-phenylethylacrylamide；(E)-3-(4-hydroxyphenyl)-N-phenethylacrylamide；N-trans-coumaroyltyramine；3-(4-Hydroxyphenyl)-N-phenethylprop-2-enamide, (E)-；(E)-3-(4-hydroxyphenyl)-N-(2-phenylethyl)prop-2-enamide
• CAS: 103197-54-2
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: GQNHFEIKUYMXAQ-DHZHZOJOSA-N

物化性质

• 沸点：
  523.9±50.0 °C(Predicted)
• 密度：
  1.169±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-苯乙胺盐酸盐 在 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 N-(2-phenylethyl)-4-hydroxycinnamamide
  参考文献：
  名称：

  Inhibition of in Vitro Prostaglandin and Leukotriene Biosyntheses by Cinnamoyl-.BETA.-phenethylamine and N-Acyldopamine Derivatives.

  摘要：

  N-反式和N-顺式-阿魏酰基酪胺是从印尼药用植物空心菜（旋花科）中分离得到的体外前列腺素（PG）合成抑制剂。为了阐明结构活性关系，合成了可能由天然存在的肉桂酸和β-苯乙胺组合得到的肉桂酰-β-苯乙胺，并测试了它们对PG合成酶和花生四烯酸5-脂氧合酶的抑制活性。含有儿茶酚基团的化合物，如N-咖啡酰基-β-苯乙胺（CaP），显示出对PG合成酶更高的抑制效果。儿茶酚基团被发现对抑制花生四烯酸5-脂氧合酶至关重要。对浓度依赖性PG生物合成效应的研究表明，CaP在较低浓度范围内增强了PG生物合成，而在较高浓度下抑制了反应。通过纯化的PG内过氧化物合成酶和微粒体PG合成酶研究了CaP对每个反应步骤的影响。CaP抑制了环氧合酶反应，同时增强了氢过氧化物酶反应。从多巴胺和脂肪酸合成了含有儿茶酚和脂溶性基团的N-酰基多巴胺，以测试它们对花生四烯酸5-脂氧合酶的抑制效果。N-亚油酰多巴胺是最活跃的化合物，在我们的测定系统中其IC50值为2.3nM，而作为5-脂氧合酶特异性抑制剂的AA 861的IC50值为8nM。

  DOI：

  10.1248/cpb.40.396

文献信息

• Discovery of caffeic acid phenethyl ester derivatives as novel myeloid differentiation protein 2 inhibitors for treatment of acute lung injury
  作者：Lingfeng Chen、Yiyi Jin、Hongjin Chen、Chuchu Sun、Weitao Fu、Lulu Zheng、Min Lu、Pengqin Chen、Gaozhi Chen、Yali Zhang、Zhiguo Liu、Yi Wang、Zengqiang Song、Guang Liang

  DOI：10.1016/j.ejmech.2017.11.066

  日期：2018.1

  Myeloid differentiation protein 2 (MD2) is an essential molecule which recognizes lipopolysaccharide (LPS), leading to initiation of inflammation through the activation of Toll-like receptor 4 (TLR4) signaling. Caffeic acid phenethyl ester (CAPE) from propolis of honeybee hives could interfere interactions between LPS and the TLR4/MD2 complex, and thereby has promising anti-inflammatory properties

  髓样分化蛋白2（MD2）是识别脂多糖（LPS）的必需分子，可通过激活Toll样受体4（TLR4）信号传导引发炎症。蜜蜂蜂巢蜂胶中的咖啡酸苯乙酯（CAPE）可能会干扰LPS与TLR4 / MD2复合物之间的相互作用，因此具有令人振奋的抗炎特性。在这项研究中，我们设计和合成了48种CAPE衍生物，并评估了它们在LPS激活的小鼠初级腹膜巨噬细胞（MPM）中的抗炎活性。发现活性最高的化合物10s以高亲和力与MD2结合，从而阻止了LPS / MD2 / TLR4复合物的形成。10s的结合模式揭示了与MD2的主要相互作用是通过两个关键的氢键和疏水相互作用建立的。此外，10s在体内对LPS引起的ALI（急性肺损伤）显示出显着的保护作用。综上所述，这项工作为开发抗炎药提供了新的先导结构和候选药物MD2抑制剂。
• Isolation and Activity of<i>N</i>-<i>p</i>-Coumaroyltyramine, an<i>α</i>-Glucosidase Inhibitor in Welsh Onion (<i>Allium fistulosum</i>)
  作者：Tetsuo Nishioka、Jun Watanabe、Jun Kawabata、Ryoya Niki

  DOI：10.1271/bbb.61.1138

  日期：1997.1

  A phenolic amide, N-p-coumaroyltyramine (1), was isolated as an α-glucosidase inhibitor from methanol extracts of Welsh onion (Allium fistulosum). The inhibitory activity of 1 against a yeast enzyme was as high as Ki 8.4 × 10−7  m. From a structure-activity relationship study of 1 and its related compounds, the occurrence of α-glucosidase inhibitory activity required a p-coumaramide structure, with an amide hydrogen and alkyl or aralkyl substituent on the amide part.

  从威尔士洋葱（Allium fistulosum）的甲醇提取物中分离出一种酚酰胺--N-对香豆酰酪胺（1），作为一种α-葡萄糖苷酶抑制剂。通过对 1 及其相关化合物的结构-活性关系研究发现，α-葡萄糖苷酶抑制活性的产生需要对香豆酰酰胺结构，酰胺部分含有酰胺氢和烷基或芳烷基取代基。
• Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition
  作者：Yeong Hun Song、Dae Wook Kim、Marcus J. Curtis-Long、Chanin Park、Minky Son、Jeong Yoon Kim、Heung Joo Yuk、Keun Woo Lee、Ki Hun Park

  DOI：10.1016/j.ejmech.2016.02.044

  日期：2016.5

  active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1–3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0

  reported藜提取物具有抑制α-葡萄糖苷酶的潜力，但至今尚无有效成分的信息。这项研究试图分离负责的代谢产物，并阐明其对α-葡萄糖苷酶的抑制机制。通过分馏T. terristris提取物，三肉桂酸酰胺衍生物（1 - 3）中确定具有对抗α葡糖苷酶的活性组分。引线结构，ñ -反式-coumaroyltyramine 1，表明α葡萄糖苷酶的抑制显著（IC 50 = 0.42μM）。此外，所有活性化合物均显示出非竞争性的抑制机制，很少有关于α-葡萄糖苷酶抑制剂的报道。通过显示K m和V max以及K ik / K iv之比在1.029至1.053之间的降低，充分证明了该动力学行为。我们进行了研究，以研究如何对铅结构进行化学修饰1可能会影响抑制。肉桂酸酰胺的A环中的α，β-不饱和羰基和羟基已成为抑制α-葡糖苷酶的关键功能。分子模型研究表明，抑制活性与酶和抑制剂之间的π-π相互作用以及氢键相互作用密切相关。
• Structure−Activity Relationship of <i>N</i>-(Phenylalkyl)cinnamides as Novel NR2B Subtype-Selective NMDA Receptor Antagonists
  作者：Amir P. Tamiz、Sui Xiong Cai、Zhang-Lin Zhou、Po-Wai Yuen、Robert M. Schelkun、Edward R. Whittemore、Eckard Weber、Richard M. Woodward、John F. W. Keana

  DOI：10.1021/jm990199u

  日期：1999.8.1

  A novel series of N-(phenylalkyl)cinnamides related to N-(4-phenylbutyl)-3,4-dihydroxy-beta-cyanocinnamide (6, an EGFR-K inhibitor with high antiproliferative activity) was synthesized and tested for antagonism at N-methyl-D-aspartate (NMDA) receptor subtypes. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The N-(phenylalkyl)cinnamides are selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, N-(4-phenylbutyl)-4-hydroxycinnamide (16) has an IC50 value of 77 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. Potency at alpha(1) adrenergic receptors is low for the four cinnamides tested. Inhibition of NR1A/2B receptors does not correlate with EGFR and ErbB2/neu tyrosine kinase inhibitor activity. The N-(phenylalkyl)cinnamide series we describe provides a novel and structurally diverse framework for designing new NR2B-selective NMDA antagonists as potential CNS therapeutics.
• Induction of adiponectin by natural and synthetic phenolamides in mouse and human preadipocytes and its enhancement by docosahexaenoic acid
  作者：Yoshimitsu Yamazaki、Yasuhiro Kawano、Masami Uebayasi

  DOI：10.1016/j.lfs.2007.11.016

  日期：2008.1

  Adiponectin, the adipose-derived cytokine, plays an important role in preventing metabolic syndromes. To develop new adiponectin inducers, eight species of ferulic esters and amides, and five related compounds were synthesized and tested on the stimulation of adiponectin production in mouse 3T3-L1 and normal human preadipocytes. The ferulamides with an aromatic ring in the N-substituent are very active in inducing adiponectin as compared with the known active compounds, curcumin, [6]-gingerol, and capsaicin, and furthermore the activities of these ferulamides are remarkably stronger than those of the corresponding esters or the straight chain octylamide. The most active compound, N-(2-phenylethyl)ferulamide (7), was found to activate the PPAR (peroxisome proliferator-activated receptor) gamma-RXR (retinoid X receptor) alpha heterodimeric complex in the PPRE (PPAR-responsive element)-driven luciferase reporter assay. The adiponectin production by 7 is synergistically enhanced by coaddition of a PPAR-gamma-specific agonist, pioglitazone (PGZ), or another PPAR gamma agonist, docosahexaenoic acid (DRA), in cultured preadipocytes. The compound 7 alone did not show a statistically significant effect on the plasma adiponectin level in KK-A(y)/Ta mice, while 1% 7 in the diets significantly lowered the blood glucose and triglyceride levels and 0.3% 7 mixed with DHA oil in the diets significantly increased the adiponectin level as compared with the control. These results suggest that the present ferulamides would be useful lead compounds in developing more potent agents for treatment of metabolic syndromes through promoting the endogenous adiponectin production, and that such an activity is possibly enhanced by the coadministration with DHA. (C) 2007 Elsevier Inc. All rights reserved.