3-(4-hydroxyphenyl)-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]prop-2-enamide | 1394285-23-4

• 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: 3-(4-hydroxyphenyl)-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]prop-2-enamide
• CAS: 1394285-23-4
• 化学式: C₂₀H₂₀N₂O₃
• 分子量: 336.39
• InChiKey: DAYQHEUNAQSDHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-甲氧基色胺 、 对羟基肉桂酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(4-hydroxyphenyl)-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]prop-2-enamide
  参考文献：
  名称：

  Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

  摘要：

  We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.

  DOI：

  10.1074/jbc.m111.307199

文献信息

• TRYPTAMINE DERIVATIVES, THEIR PREPARATION AND THEIR USE IN GASTROPATHY
  申请人：Bandyopadhyay Uday

  公开号：US20130197052A1

  公开（公告）日：2013-08-01

  The synthesis and evaluation of gastroprotective effect of different tryptamine derivatives. Tryptamine derivatives have been synthesized by formation of amide or ester with some known anti oxidant molecules. These derivatives show excellent antioxidant property in vitro. Among all the derivatives the compound SEGA (3a), that was prepared by the combination of serotonin with gallic acid shows the greater antioxidant property than the other synthesized compounds both in vivo and in vitro. SEGA(3a) shows the gastroprotective effect against NSAIDs (indomethacin or diclofenac)-induced gastropathy in dose dependent manner and also accelerates the healing from injury. It prevents the NSAIDs-induced mitochondrial oxidative stress in vivo. This derivative prevents NSAID-induced mitochondrial oxidative stress-mediated apoptosis in vivo by preventing the activation of caspase 9 and caspase-3 and restores NSAIDs-mediated collapse of mitochondroial transmembrane potential and dehydrogenase activity. SEGA (3a) plays an important role as an iron chelator as well as intra mitochondrial ROS scavenger. Thus, SEGA (3a) is a potent antioxidant antiapototic molecule, which efficiently prevents NSAID-induced gastropathy and stress or alcohol-mediated gastric damage.

  不同色胺衍生物的合成和胃保护效果的评估。色胺衍生物通过与一些已知抗氧化分子形成酰胺或酯而被合成。这些衍生物在体外表现出优秀的抗氧化性能。在所有衍生物中，通过将血清素与没食子酸结合而制备的SEGA（3a）化合物在体内和体外都表现出比其他合成化合物更强的抗氧化性能。SEGA（3a）呈剂量依赖性地显示对NSAIDs（消炎药，如消炎痛或双氯芬酸）诱导的胃病的胃保护作用，并且加速了受伤部位的愈合。它预防了NSAIDs诱导的体内线粒体氧化应激。该衍生物通过阻止caspase 9和caspase-3的激活，恢复NSAIDs介导的线粒体跨膜电位崩溃和脱氢酶活性，从而预防了NSAIDs诱导的线粒体氧化应激介导的凋亡。SEGA（3a）不仅作为铁螯合剂，还作为线粒体内ROS清除剂起作用。因此，SEGA（3a）是一种有效预防NSAID诱导的胃病以及压力或酒精介导的胃损伤的抗氧化抗凋亡分子。
• [EN] TRYPTAMINE DERIVATIVES, THEIR PREPARATION AND THEIR USE IN GASTROPATHY<br/>[FR] DÉRIVÉS DE TRYPTAMINE, LEUR PRÉPARATION ET LEUR UTILISATION DANS UNE GASTROPATHIE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2012035406A1

  公开（公告）日：2012-03-22

  The present invention concerns the synthesis and evaluation of gastroprotective effect of different tryptamine derivatives. Tryptamine derivatives have been synthesized by formation of amide or ester with some known anti oxidant molecules. These derivatives show excellent antioxidant property in vitro. Among all the derivatives the compound SEGA (3 a), that was prepared by the combination of serotonin with gallic acid shows the greater antioxidant property than the other synthesized compounds both in vivo and in vitro. SEGA(3a) shows the gastroprotective effect against NSAIDs (indomethacin or diclofenac)-induced gastropathy in dose dependent manner and also accelerates the healing from injury. It prevents the NSAIDs-induced mitochondrial oxidative stress in vivo. This derivative prevents NSAID-induced mitochondrial oxidative stress-mediated apoptosis in vivo by preventing the activation of caspase 9 and caspase-3 and restores NSAIDs-mediated collapse of mitochondroial transmembrane potential and dehydrogenase activity. SEGA (3 a) plays an important role as an iron chelator as well as intra mitochondrial ROS scavenger. Thus, SEGA (3 a) is a potent antioxidant antiapototic molecule, which efficiently prevents NSAID-induced gastropathy and stress or alcohol -mediated gastric damage.

  本发明涉及合成和评估不同色胺衍生物的胃保护效果。色胺衍生物通过与一些已知的抗氧化分子形成酰胺或酯而被合成。这些衍生物在体外表现出优秀的抗氧化性能。在所有的衍生物中，通过将血清素与没食子酸结合制备的SEGA（3a）表现出比其他合成化合物更强的抗氧化性能，无论是在体内还是在体外。SEGA（3a）显示出对NSAIDs（消炎药，如消炎痛或双氯芬酸）诱导的胃病的剂量依赖性胃保护作用，并且加速受伤后的愈合。它可以预防NSAIDs诱导的体内线粒体氧化应激。该衍生物通过阻止caspase 9和caspase-3的活化，恢复NSAIDs介导的线粒体跨膜电位和脱氢酶活性的崩溃，从而预防NSAID诱导的线粒体氧化应激介导的凋亡。SEGA（3a）作为铁螯合剂和线粒体内ROS清除剂发挥重要作用。因此，SEGA（3a）是一种强效的抗氧化抗凋亡分子，有效预防NSAID诱导的胃病和压力或酒精介导的胃损伤。
• US8901317B2
  申请人：——

  公开号：US8901317B2

  公开（公告）日：2014-12-02
• Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy
  作者：Chinmay Pal、Samik Bindu、Sumanta Dey、Athar Alam、Manish Goyal、Mohd. Shameel Iqbal、Souvik Sarkar、Rahul Kumar、Kamal Krishna Halder、Mita Chatterjee Debnath、Susanta Adhikari、Uday Bandyopadhyay

  DOI：10.1074/jbc.m111.307199

  日期：2012.1

  We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.