4-hydroxy-3-methoxycinnamic acid n-octylamide | 150058-99-4

• 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: 4-hydroxy-3-methoxycinnamic acid n-octylamide
• 英文别名: N-(1-octyl)ferulamide；AP-004；(E)-3-(4-hydroxy-3-methoxyphenyl)-N-octylprop-2-enamide
• CAS: 150058-99-4
• 化学式: C₁₈H₂₇NO₃
• 分子量: 305.417
• InChiKey: CNZGHLAXLFAZJR-ZRDIBKRKSA-N

物化性质

• 沸点：
  498.2±45.0 °C(Predicted)
• 密度：
  1.050±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxy-3-methoxycinnamic acid n-octylamide 以 甲醇 为溶剂， 反应 48.0h， 以40%的产率得到(Z)-N-octyl-4-hydroxy-3-methoxycinnamamide
  参考文献：
  名称：

  Analogs of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"

  摘要：

  Structural variants of the hydrophobic side chain (''C region'') of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (Ca-45(2+) influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, <55) in order to obtain high potency. Combination of the information gained here about the ''C-region'' of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.

  DOI：

  10.1021/jm00068a016
• 作为产物：
  描述：

  (E)-N-octyl-4-acetoxy-3-methoxycinnamamide 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 4-hydroxy-3-methoxycinnamic acid n-octylamide
  参考文献：
  名称：

  Induction of adiponectin by natural and synthetic phenolamides in mouse and human preadipocytes and its enhancement by docosahexaenoic acid

  摘要：

  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.

  DOI：

  10.1016/j.lfs.2007.11.016

文献信息

• Stimulation of Sarcoplasmic Reticulum Ca2+-ATPase by Gingerol Analogues.
  作者：Yasushi OHIZUMI、Susumu SASAKI、Kazuki SHIBUSAWA、Kiyofumi ISHIKAWA、Fumihiko IKEMOTO

  DOI：10.1248/bpb.19.1377

  日期：——

  We have reported previously that [8]-gingerol increased Ca2+-ATPase activity. 1, 2)Here we synthesized gingerol related compounds (AP-004, AP-005 and AP-015) and investigated the effects of gingerols ([6]-gingerol, [8]-gingerol and [10]-gingerol) and the synthesized compounds on the Ca2+-ATPase activity of sarcoplasmic reticulum (SR). The Ca2+-ATPase activity and the Ca2+-pumping activity increased by these compounds in a concentration-dependent manner. It is probable that both the o-methoxyphenol and hydrocarbon chain in the molecule of gingerol analogues are necessary for the activation of the Ca2+-pumping ATPase activity of SR.

  我们之前报道过 [8]-姜酚可增加 Ca2+-ATPase 活性。 1, 2)在这里，我们合成了姜辣素相关化合物（AP-004、AP-005和AP-015）并研究了姜辣素（[6]-姜辣素、[8]-姜辣素和[10]-姜辣素）的作用和合成了对肌浆网 (SR) Ca2+-ATPase 活性的化合物。这些化合物以浓度依赖性方式增加Ca2+-ATP酶活性和Ca2+泵活性。姜酚类似物分子中的邻甲氧基苯酚和烃链很可能对于激活 SR 的 Ca2+ 泵 ATP 酶活性是必需的。
• Synthesis of amide compounds of ferulic acid, and their stimulatory effects on insulin secretion in vitro
  作者：Eisaku Nomura、Ayumi Kashiwada、Asao Hosoda、Kozo Nakamura、Hideko Morishita、Takuo Tsuno、Hisaji Taniguchi

  DOI：10.1016/s0968-0896(03)00280-3

  日期：2003.8

  We prepared amide compounds which were derived from ferulic acid using various amines, and investigated their stimulatory effects on insulin secretion using rat pancreatic RIN-5F cells. Most of these compounds exhibited significant promotion of the insulin-release at a concentration of 10 muM and in particular, the amides having n-butyl, n-pentyl, pyrrolidine, and piperidine groups showed high activity. (C) 2003 Elsevier Ltd. All rights reserved.
• Analogs of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"
  作者：Christopher S. J. Walpole、Roger Wrigglesworth、Stuart Bevan、Elizabeth A. Campbell、Andy Dray、Iain F. James、Kay J. Masdin、Martin N. Perkins、Janet Winter

  DOI：10.1021/jm00068a016

  日期：1993.8

  Structural variants of the hydrophobic side chain (''C region'') of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (Ca-45(2+) influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, <55) in order to obtain high potency. Combination of the information gained here about the ''C-region'' of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.
• 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.