[(1H-indol-3-yl)methyl][2-(5-methoxy-1H-indol-3-yl)ethyl]amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [(1H-indol-3-yl)methyl][2-(5-methoxy-1H-indol-3-yl)ethyl]amine
• 英文别名: N-(1H-indol-3-ylmethyl)-2-(5-methoxy-1H-indol-3-yl)ethanamine
• 化学式: C₂₀H₂₁N₃O
• 分子量: 319.406
• InChiKey: RRWSHAMNKJKMFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.8
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-甲氧基吲哚-3-甲醛 在 aluminum (III) chloride 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 formamide 作用下， 以 甲醇 、 乙醚 为溶剂， 生成 [(1H-indol-3-yl)methyl][2-(5-methoxy-1H-indol-3-yl)ethyl]amine
  参考文献：
  名称：

  N-Skatyltryptamines—Dual 5-HT6R/D2R Ligands with Antipsychotic and Procognitive Potential

  摘要：

  合成了一系列N-斯卡提尔色胺类化合物，并确定了它们对5-羟色胺和多巴胺受体的亲和力。这些化合物对5-HT1A、5-HT2A、5-HT6和D2受体表现出活性。通过同源建模鉴定并研究了导致亲和力/活性变化的取代模式。选择的化合物被筛选以确定它们的代谢、渗透性、肝毒性和CYP抑制作用。鉴定了几种具有额外5-HT6R拮抗剂和激动剂特性的D2受体拮抗剂。前者的组合类似于已知的抗精神病药物，而后者尤为有趣，因为以前尚未进行研究。先前已经显示，选择性的5-HT6R拮抗剂在几种啮齿动物模型中产生了促认知和促记忆效应。5-HT6R激动剂的给药效果更加模棱两可——在原始动物中，它不会改变记忆或产生轻微的遗忘效应，而在记忆障碍的啮齿动物模型中，它们像拮抗剂一样改善了状况。使用鉴定出的化合物15和18，我们尝试区分表现出D2R拮抗功能与5-HT6R激动作用相结合的配体，以及在小鼠精神病模型中混合D2/5-HT6R拮抗剂。

  DOI：

  10.3390/molecules26154605

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
• N-Skatyltryptamines—Dual 5-HT6R/D2R Ligands with Antipsychotic and Procognitive Potential
  作者：Agata Hogendorf、Adam S. Hogendorf、Rafał Kurczab、Grzegorz Satała、Bernadeta Szewczyk、Paulina Cieślik、Gniewomir Latacz、Jadwiga Handzlik、Tomasz Lenda、Katarzyna Kaczorowska、Jakub Staroń、Ryszard Bugno、Beata Duszyńska、Andrzej J. Bojarski

  DOI：10.3390/molecules26154605

  日期：——

  A series of N-skatyltryptamines was synthesized and their affinities for serotonin and dopamine receptors were determined. Compounds exhibited activity toward 5-HT1A, 5-HT2A, 5-HT6, and D2 receptors. Substitution patterns resulting in affinity/activity switches were identified and studied using homology modeling. Chosen hits were screened to determine their metabolism, permeability, hepatotoxicity, and CYP inhibition. Several D2 receptor antagonists with additional 5-HT6R antagonist and agonist properties were identified. The former combination resembled known antipsychotic agents, while the latter was particularly interesting due to the fact that it has not been studied before. Selective 5-HT6R antagonists have been shown previously to produce procognitive and promnesic effects in several rodent models. Administration of 5-HT6R agonists was more ambiguous—in naive animals, it did not alter memory or produce slight amnesic effects, while in rodent models of memory impairment, they ameliorated the condition just like antagonists. Using the identified hit compounds 15 and 18, we tried to sort out the difference between ligands exhibiting the D2R antagonist function combined with 5-HT6R agonism, and mixed D2/5-HT6R antagonists in murine models of psychosis.

  合成了一系列N-斯卡提尔色胺类化合物，并确定了它们对5-羟色胺和多巴胺受体的亲和力。这些化合物对5-HT1A、5-HT2A、5-HT6和D2受体表现出活性。通过同源建模鉴定并研究了导致亲和力/活性变化的取代模式。选择的化合物被筛选以确定它们的代谢、渗透性、肝毒性和CYP抑制作用。鉴定了几种具有额外5-HT6R拮抗剂和激动剂特性的D2受体拮抗剂。前者的组合类似于已知的抗精神病药物，而后者尤为有趣，因为以前尚未进行研究。先前已经显示，选择性的5-HT6R拮抗剂在几种啮齿动物模型中产生了促认知和促记忆效应。5-HT6R激动剂的给药效果更加模棱两可——在原始动物中，它不会改变记忆或产生轻微的遗忘效应，而在记忆障碍的啮齿动物模型中，它们像拮抗剂一样改善了状况。使用鉴定出的化合物15和18，我们尝试区分表现出D2R拮抗功能与5-HT6R激动作用相结合的配体，以及在小鼠精神病模型中混合D2/5-HT6R拮抗剂。